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1. Sharyn Alfonsi – Sharyn Alfonsi is an American journalist and correspondent for 60 Minutes and 60 Minutes Sports. She made her appearance on 60 Minutes on CBS on March 1,2015. Alfonsi attended high school in McLean, Virginia and she graduated with honors from the University of Mississippi in Oxford in 1994, where she was a James Love Scholar. Alfonsi began her career in broadcast journalism at KHBS-TV in Fort Smith, Arkansas from 1994–95 and she then became a general assignment reporter for WVEC–TV in Norfolk, Virginia from 1995–97, where she traveled with the military. Between 1998-2000, she worked as a reporter and substitute anchor for KIRO-TV in Seattle, Washington, Alfonsi was named a CBS News correspondent, based in New York City, in July 2004. She also anchored the CBS Evening News and she has traveled to cover stories including the wars in Iraq, Afghanistan, the conflict in Israel, Hurricane Katrina, and the Sago Mine Disaster in West Virginia. Alfonsi had a near-miss in Israel when a missile landed close to her shelter and she was the lead reporter covering the Virginia Tech Massacre. She was one of several correspondents who departed the network after Katie Couric took over the chair from Schieffer in September 2006. Bob Schieffer called Alfonsi a true treasure of the network, despite the 30 year age difference, the two are often seen dining together in New York. Template, New York Post On August 10,2006, Alfonsi was featured on CBSs Public Eye blog, on January 28,2008, it was announced that Alfonsi would join ABC News as a New York-based correspondent for World News with Charles Gibson and Good Morning America. Alfonsi has occasionally anchored Good Morning America and World News, in 2012, she left ABC to return to CBS News and join the cast of 60 Minutes Sports. 60 Minutes Sports premiered in January 2012 on the Showtime Network and she has anchored the CBS This Morning with Charlie Rose, Norah ODonnell, and Gayle King and filled in as an anchor for Scott Pelley on the CBS Evening News. Alfonsi made her appearance on 60 Minutes on March 1,2015 with an investigative story about fraud after Hurricane Sandy. She appeared multiple time in the 2016 season, including a piece on hacking phones that showed how hackers could easily access a Congressmans phone. In May 2013, Alfonsi gave the commencement address at the Meek School of Journalism and her speech was named by NPR as one of The Best Commencement Speeches Ever

2. Craig Allen (meteorologist) – Craig Allen is a meteorologist whose weather reports can be heard weekdays on WCBS Newsradio 880 in New York City and internationally at WCBS880. com. Allen previously worked for WCBS-TV until September 2006 and CBS This Morning, Allen is a graduate of Farmingdale High School. He earned his bachelors degree from Stony Brook University in 1979 and has been the chief meteorologist on WCBS since 1981, on January 11,2007, Allen joined News 12 Long Island as a fill-in meteorologist. On June 2,2007, Allen began filling in as anchor on WNYW. By the end of 2007, Allen continued his role as Fox 5s weekend meteorologist since the departure of Tracy Humphrey. In September 2008, he was named weekend meteorologist and primary fill in for Nick Gregory, fox5 replaced him with meteorologist Shay Ryan but allowed him to freelance as needed. On April 27,2011, Allen began his 30th year with WCBS-AM/880, Allen joined WPIX-TV in May 2010 and is now the regular weekend meteorologist for the WPIX5 &10 pm newscasts with Kaity Tong. He also covers for Mr. G on weekdays, Allen also added additional radio duties for CBS Radio News, providing information, data and forecasts for the radio network

3. Serena Altschul – Serena Altschul is an American broadcast journalist, well known for her work at MTV News. Altschul was born in New York City, and is the daughter of author and botanist Siri von Reis and Arthur Altschul and her mother is of half-Finnish and half-Swedish ancestry and her father is of Jewish ancestry. When her parents divorced, two-year-old Serena and her two siblings were raised by their mother and her brother, Arthur Altschul, Jr. is married to journalist Rula Jebreal and her sister, Emily Helen Altschul, is married to journalist John Miller. She also has two half-brothers, Charles Altschul and mathematician Stephen Altschul from her fathers previous marriage, Altschul attended Scripps College for a couple of years, studying English literature, but did not graduate. While in college, she was the producer of 1993s The Last Party. After school, she worked for two years at Channel One News, a channel seen nationwide in schools, as an anchor/reporter. In 1995 she landed a job at MTV and in January 1996 she started working for MTV News and she also hosted shows such as MTV News, UNfiltered, Breaking it Down and hosted and produced True Life. From 2002 to 2003 Altschul worked at CNN and she hosted and produced a CNN special on the return of PCP. She continued working at MTV News while at CNN, on December 23,2003, she was named a CBS News contributing correspondent. She now appears on CBS Sunday Morning and she played herself on Jay-Zs 1999 song, Dope Man. She also appeared as herself in the films Queen of the Damned and Josie and the Pussycats

4. Christiane Amanpour – Christiane Amanpour, CBE is a British-Iranian journalist and television host. Amanpour is the Chief International Correspondent for CNN and host of CNN Internationals nightly interview program Amanpour, Amanpour is also a Global Affairs Anchor of ABC News. In 2013, she moved from New York City to live permanently in London, England, with her husband, former US Assistant Secretary of State James Rubin, born in London, England, Amanpour was raised in Tehran. Her father, Mahmoud Amanpour, is a Muslim from Iran, her mother and she is fluent in English and Persian. After completing the larger part of her education in Iran. She attended Holy Cross Convent, a school located in Chalfont St. Peter, Buckinghamshire. Christiane and her returned to England not long after the Islamic Revolution began. She has stressed that they were not forced to leave the country, the family ultimately remained in England, finding it difficult to return to Iran. After leaving New Hall, Amanpour moved to the United States to study journalism at the University of Rhode Islands Harrington School of Communication, during her time there, she worked in the news department at WBRU-FM in Providence, Rhode Island. She also worked for NBC affiliate WJAR in Providence, Rhode Island, in 1983, Amanpour graduated from the university summa cum laude and Phi Beta Kappa with a B. A. degree in journalism. In 1983, she was hired by CNN on the desk in Atlanta, Georgia. In 1989, she was assigned to work in Frankfurt, Germany, through this position, she was able to move up in the company and by 1990 served as a correspondent for CNNs New York bureau. Following Iraqs occupation of Kuwait in 1990, Amanpours reports of the Persian Gulf War brought her wide notice while also taking the network to a new level of news coverage, thereafter, she reported from the Bosnian war and other conflict zones. Objectivity doesnt mean treating all sides equally and it means giving each side a hearing. Amanpour gained a reputation for being fearless during the Gulf and Bosnian wars, from 1992 to 2010, Amanpour was CNNs chief international correspondent as well as the anchor of Amanpour, a daily CNN interview program that aired 2009–2010. After 9/11, she was the first international correspondent to interview British Prime Minister Tony Blair, French President Jacques Chirac, additional interview partners are Hillary Clinton, Nicolás Maduro, Hassan Rouhani and Moammar Gadhafi. She also conducted interviews with Constantine II of Greece, Reza Pahlavi, Ameera al-Taweel, from 1996 to 2005, she was contracted by 60 Minutes creator Don Hewitt to file four to five in-depth international news reports a year as a special contributor. These reports garnered her a Peabody Award in 1998, hewitts successor Jeff Fager was not a fan of her work and terminated her contract

5. Jennifer Ashton – Jennifer Lee Ashton is a physician, author and television medical contributor. She is the Chief Womens Health Correspondent for ABC News and Good Morning America and is a columnist for Cosmopolitan Magazine, Ashton is a frequent guest speaker and moderator for public events including Women and Heart Disease, Ovarian Cancer Awareness, and Womens Health and Fertility. Ashton was born in California to Dr. Oscar Garfein, a New York City cardiologist, and Dorothy Garfein and her brother, Dr. Evan Garfein is the Chief of Plastic and Reconstructive Surgery at Montefiore Hospital in New York City. She attended Horace Mann School in Riverdale, New York City, in 1991, she graduated from Columbia College, Columbia University, with a bachelors in art history. Her medical degree is from Columbia College of Physicians and Surgeons of Columbia University in 2000, in 2016, she received her Masters of Science Degree in Nutrition from Columbia University. Ashton practices as a board-certified Obstetrician & Gynecologist at Hygeia Gynecology, LLC and she served her residency at St. Lukes–Roosevelt Hospital Center in New York. She has also been a physician at Englewood Hospital and Medical Center. Ashton is the author of three books, many articles in a variety of magazines, and contributed to a blog for The Record, of Bergen. Her first book, The Body Scoop for Girls, published in 2009 and her second book, Your Body Beautiful, published in 2012, is book about health and wellness for women in their middle life. She appeared in The Learning Channels A Baby Story, on PBS, in April 2009, Ashton started as CBS News medical correspondent. In January 2012, Ashton began as co-host of ABCs short lived The Revolution which was canceled in April 2012 due to poor viewership, in October 2013, she also joined the staff on the daytime medical talk show The Doctors. Starting December 2013, Dr. Ashton returned to school in pursuit of a degree in nutrition from Columbia University. In January 2017, Ashton divorced from Dr. Robert Ashton Jr. a thoracic and they have two children, Alex and Chloe. In 2014 she stated she had learned Transcendental Meditation through the David Lynch Foundation, Ashton is an avid sports fan and has shown her support for the NHL on multiple social media platforms. On February 11,2017, Dr. Robert Ashton,52 and his death came two weeks after his divorce from Dr. Jennifer Ashton,47, according to the Fort Lee Daily Voice. The Body Scoop for Girls, A Straight-Talk Guide to a Healthy, Beautiful You, by Jennifer Ashton M. D. Ob-Gyn with Christine Larson,2009, ISBN 1-5833-3458-0. Your Body Beautiful, Clockstopping Secrets to Staying Healthy, Strong, and Sexy in Your 30s, 40s, and Beyond, by Jennifer Ashton M. D. Ob-Gyn with Christine Rojo,2012, ISBN 1-5833-3458-0. Eat This When Youre Expecting, Not That, Your Complete Guide to the Very Best Foods For Every Stage of Pregnancy, by Americas leading OB/GYN Jennifer Ashton, MD and David Zinczenko,2016

6. Sharyl Attkisson – She was formerly an investigative correspondent in the Washington bureau for CBS News. She had also substituted as anchor for the CBS Evening News and she resigned from CBS News on March 10,2014 after 21 years with the network. Attkisson was born in 1961 in Sarasota, Florida and her step-father is an orthopedic surgeon, and her brother is an emergency room physician. Attkisson graduated from the University of Florida with a degree in broadcast journalism in 1982, Attkisson began her broadcast journalism career in 1982, aged 22, as a reporter at WUFT-TV, the PBS station in Gainesville, Florida. She later worked as an anchor and reporter at WTVX-TV Fort Pierce/West Palm Beach, Florida from 1982–1985, WBNS-TV, the CBS affiliate in Columbus, Ohio from 1985–86, and WTVT Tampa, Florida. From 1990–1993, Attkisson was an anchor for CNN, and also served as a key anchor for CBS space exploration coverage in 1993. Attkisson left CNN in 1993, moving to CBS, where she anchored the news broadcast CBS News Up to the Minute and became an investigative correspondent based in Washington. She served on the University of Floridas Journalism College Advisory Board and was its chair in 1996, the University gave her an Outstanding Achievement Award in 1997. From 1997 to 2003, Attkisson simultaneously hosted CBS News Up to the Minute, Attkisson received an Investigative Reporters and Editors Finalist award for Dangerous Drugs in 2000. In 2001, Attkisson received an Investigative Emmy Award nomination for Firestone Tire Fiasco from the National Academy of Television Arts and Sciences. In 2002, she co-authored a college textbook, Writing Right for Broadcast and Internet News, the award was presented in New York City on September 10,2002. Attkisson was part of the CBS News team that received RTNDA-Edward R. Murrow Awards in 2005 for Overall Excellence, in 2006, Attkisson served as Capitol Hill correspondent for CBS, as one of a small number of female anchors covering the 2006 midterms. Attkisson was part of the CBS News team that received RTNDA-Edward R. Murrow Awards in 2008 for Overall Excellence. In 2008, Attkisson reported that a claim by Hillary Clinton to have dodged sniper fire in Bosnia was unfounded, Clintons trip to Bosnia was risky, Attkisson said, Attkisson was on the trip with Clinton. The day after Attkissons report on the CBS Evening News, Clinton admitted there was no sniper fire, in 2009, Attkisson won an Investigative Emmy Award for Business and Financial Reporting for her exclusive reports on the Troubled Asset Relief Program and the bank bailout. The award was presented on December 7 at Fordham Universitys Lincoln Center Campus in New York City, Attkisson returned to the University of Florida as a keynote speaker at the College of Journalism and Communications in 2010. In 2011, Paul Offit criticized Attkissons vaccine-skeptic reporting in his book Deadly Choices as damning by association, dr. Offit has been criticized for providing false information about Attkisson and his vaccine industry ties. In 2012, CBS News accepted an Investigative Reporting Award given to Attkissons reporting on ATFs Fast, the award was from Accuracy in Media, a non-profit news media watchdog group, and was presented at a Conservative Political Action Conference

7. Jim Axelrod – Jim Axelrod is a National Correspondent and reporter for CBS News, and reports for all CBS News programs. Axelrod was one of CBS News embedded correspondents in Iraq and was the first TV reporter to broadcast live from Saddam International Airport after its takeover by American forces, Axelrod was born in New Brunswick, New Jersey. Raised in Highland Park, New Jersey, he attended Highland Park High School and he received a B. A. in 1985 from Cornell University in history and an M. A. in 1989 from Brown University, also with a major in history. Axelrod resides in Montclair, New Jersey, with his wife and their three children

8. Errol Barnett – Errol Barnett is a British-born American anchor and correspondent for CBS News based in Washington D. C. He previously anchored CNN Newsroom during overnight hours in the U. S. after hosting CNN Internationals cultural affairs program Inside Africa, during his two years at the helm of the award-winning show Barnett reported from 22 countries including Senegal, Morocco, Ethiopia and Madagascar. He was profiled in GQ South Africa in May 2013 and asked about his extensive journeys, Barnett was born in Milton Keynes, England to Pamela and Michael Christie. He has one brother, Danny Christie. His mother was remarried to Gary Barnett, a US Air Force sergeant who served in the Gulf War. The family relocated to the city of Phoenix in Arizona, Barnett was educated at Garden Lakes Elementary School and Westview High School, a public high school in Avondale, Arizona, before being hired by Channel One News and relocated to Los Angeles. In 2008, Barnett received a bachelor of degree in political science with a focus on international relations from the University of California. He was a member of the business fraternity Alpha Kappa Psi and was profiled in The Daily Bruin in April 2007, while a student at UCLA, he also worked as a correspondent and host on movie-centric cable network channel ReelzChannel. After graduation in July,2008 Barnett was hired by CNN International, in 2001, the in-school program Channel One News hired Barnett as an anchor/reporter. He was their youngest at the age of 18 and worked alongside Maria Menounos, Seth Doane, Barnett was chosen as one of Teen People magazines 20 Teens Who Will Change The World for his early work. He left Channel One News in 2006 after being accepted to UCLA to finish his undergraduate studies, CNN International hired Barnett as an anchor and correspondent in 2008, days after he graduated from UCLA. He initially reported on the rise in influence of media sites like Facebook and Twitter and anchored ‘World Report’. He was also part of the most viewed event in history during U. S. President Obamas Inauguration on CNN. com. As an anchor and correspondent for CNN International based in Atlanta, Georgia, Barnett has anchored coverage of the Ferguson, Missouri protests, the death of Robin Williams and he was previously a CNN correspondent based at CNNs bureau in the city of Johannesburg, in South Africa. While there, he covered the death of President Nelson Mandela, the Oscar Pistorius murder trial, various miner strikes, in 2010, he anchored a live noon eastern news-hour on CNN International from CNN Abu Dhabi which focused on the beginnings of the Arab Spring. In June 2016, Barnett joined CBS News as a Washington, D. C. -based Correspondent appearing on CBS This Morning and he has reported on the U. K. Brexit vote, coup attempt in Turkey and U. S. presidential race. Barnett regularly moderates panel discussions and speaks at conferences on the topics of innovation in journalism, U. S. politics, events include, NABJ/NAHJ Conference, Washington, D. C. Viewers noted Barnetts response to his co-anchors suggestion that use water cannons on demonstrators

9. Rita Braver – Rita Braver is a correspondent for CBS News. Rita Lynn Braver was born to a Jewish family in April 1948 and raised in Silver Spring and her father died while she was a teenager. She has two sisters, Bettie Braver Sugar and Sharon Braver Cohen, from 1983 to 1993, Braver served as CBS Newss chief law correspondent. She broke the story of the John Walker spy ring, as well as that of another spy and she also led CBSs coverage of the Iran-Contra affair. She served as CBSs chief White House correspondent during Bill Clintons first term, on April 10,1972, she married Washington, D. C. lawyer Robert B. Barnett whom she met in college. They have a daughter, Meredith Jane Barnett, Meredith married Dr. Daniel Ross Penn in a Jewish ceremony in Washington D. C, huffington Post - Rita Braver Profile at CBS News Appearances on C-SPAN

10. Cecil Brown (journalist) – Cecil Brown was a war correspondent who worked closely with Edward R. Murrow during World War II. He was the author of the book Suez to Singapore, which describes the sinking of HMS Repulse in December 1941 and he also has a star on the Hollywood Walk of Fame for his contribution to radio. Brown was born September 14,1907 in New Brighton, Pennsylvania, after graduating from Ohio State University in 1929, Brown left the United States for the Mediterranean and Black Seas where he worked as a seaman. He eventually returned to the United States where he worked as a journalist at several small newspapers, by 1937 he was back in Europe working as a freelancer. CBS hired Brown in 1940 as their correspondent in Rome, where he criticized the regime of Benito Mussolini. In 1941 the Italian government cited Browns continued hostile attitude and expelled him from the country, after his expulsion from Italy, CBS sent Brown to Singapore. On December 10,1941 at 03,13 GMT the capital ships of Force Z were subjected to an aerial attack by land based Japanese bomber aircraft. Repulse was sunk at 04,33 GMT, followed by the crippled Prince of Wales at 05,13 GMT, of 1309 sailors on board Repulse, Brown was one of only 513 survivors. His experiences in his journey and dealings with Italian, British. His criticism of the British in Singapore caused him to have his war corresponent credentials revoked and he narrowly escaped from Singapore before its fall to the Japanese. He was part of a group of reporters known as Murrows Boys. In September 1943, Brown resigned from CBS after being rebuked by CBS news director Paul White for expressing an editorial opinion during an August 25 news broadcast, Brown had stated that a good deal of the enthusiasm for this war is evaporating into thin air. Announcing his resignation Brown said that he could not subscribe to what he characterized as CBS policy of non-opinionated news, after leaving CBS Brown covered the rest of the war at home, in the United States, for the Mutual Network. When World War II ended Brown continued to work in broadcast journalism as a correspondent for Mutual and he retired from broadcasting in 1967 and went to work as a professor of communication arts at Cal Poly Pomona where he worked until he died in 1987

11. Mika Brzezinski – Mika Emilie Leonia Brzezinski is an American television host, author and political commentator. Brzezinski co-hosts MSNBCs weekday morning broadcast Morning Joe with former Republican representative Joe Scarborough and she is the daughter of Zbigniew Brzezinski, the National Security Advisor to President Jimmy Carter and counselor to President Lyndon B. Johnson. Brzezinski was born in New York City, the daughter of Polish-born foreign policy expert and former National Security Advisor Zbigniew Brzezinski and her mother, of Czech descent, is a grandniece of Czechoslovakias former president Edvard Beneš. Her brother, Mark Brzezinski, is an American diplomat and was the United States Ambassador to Sweden from 2011 to 2015 and her brother is military expert Ian Brzezinski. She is also first cousin of author Matthew Brzezinski, Brzezinski attended The Madeira School during her high school years. She graduated in 1989 from Williams College in Williamstown, Massachusetts, Brzezinski began her journalism career as an assistant at ABCs World News This Morning in 1990. A year later, she moved to Tribune-owned Fox affiliate WTIC-TV/WTIC-DT in Hartford, there, she progressed from assignment and features editor to general assignments reporter. In 1992, she joined CBS affiliate WFSB-TV/WFSB-DT in Hartford and quickly progressed through the ranks to become its weekday morning anchor in 1995. In 1997, she left that role to join the CBS network news, in 2001, Brzezinski began a short hiatus from CBS News, during which she worked for rival MSNBC on the weekday afternoon show, HomePage, with co-anchors Gina Gaston and Ashleigh Banfield. Entertainment Weekly described the trio as the Powerpuff Girls of journalism and she returned to CBS News as a correspondent in September 2001, a move that thrust her into the limelight as a principal Ground Zero reporter for the September 11,2001 attacks. Brzezinski was broadcasting live from the scene when the South Tower collapsed, in her last position at CBS News, Brzezinski served as a CBS News correspondent, substitute anchor, and segment anchor for breaking news segments and routine updates. During this period she became a contributor to CBS Sunday Morning and 60 Minutes. She was subsequently fired by CBS, Brzezinski returned to MSNBC on January 26,2007, doing the evening Up To The Minute news updates. Then she worked primetime newsbreaks during the week and she also filed occasional reports for NBC Nightly News and appeared as an occasional anchor on Weekend Today. Brzezinski resigned from both shows on the eve of an option, said Brzezinski, when Scarborough selected her to co-host on Morning Joe. Brzezinski said, I struggled to keep up with the live interaction broadcasting format at 6-9 am, I became more comfortable when I found myself having a primary function of reading the prompt for lead-ins and breaks. Mika, the hot anchor was born, the producers slowly encouraged my participation in news reader segments that I was more at ease with. Geist and Joe slowly found me a capable news reader and the expansion of my role was a process, I was not pleased with the reference to being the hot anchor

12. Gretchen Carlson – Gretchen Elizabeth Carlson is an American television commentator and author. Carlson was crowned the 1989 Miss America while representing her state of Minnesota. She graduated from Stanford University with honors before embarking on a career in television, gaining experience as anchor and reporter for several local network affiliates, she joined CBS News as a correspondent in 2000 and became the co-host of the Saturday edition of The Early Show. In 2005, she moved to Fox News Channel and became the co-host of the morning show Fox & Friends along with Steve Doocy, in 2013, she announced her departure from Fox & Friends and soon thereafter launched a new program called The Real Story with Gretchen Carlson. Her autobiography, Getting Real, was published in 2015 by Viking and her contract with Fox News expired on June 23,2016. On July 6, she filed a lawsuit against then Fox News Chairman, subsequently, dozens of other women also stepped forward to accuse Ailes of harassment, and Ailes was forced to resign under pressure. In September 2016, Carlson and 21st Century Fox Corporation settled the lawsuit for $20 million, Carlson was raised in a Lutheran family in Anoka, Minnesota, the daughter of Karen Barbara and Lee Roy Carlson. Her father owned a car dealership with her uncle and she has two brothers and one sister. Her grandfather was the pastor of the then second-largest Lutheran church in the United States and she graduated from Anoka-Hennepin School District 11s Anoka High School, where she was a 1984 class valedictorian. One of her childhood nannies was Michele Bachmann, the future Republican congresswoman, growing up, Carlson was an accomplished violinist, winning numerous local and national competitions. She performed as a soloist with the Minnesota Orchestra as an 8th grader and was the concertmistress for the Greater Twin Cities Youth Symphony and she spent five summers studying at the prestigious Aspen Music Festival and School in Aspen, Colorado. Winner of several competitions at the MacPhail Center for Music in Minneapolis. In 1984, Carlson was elected as one of the Anoka Homecoming attendants and she won the title of Miss Minnesota in 1988 and became the third woman from Minnesota to win the Miss America title. For the talent competition, she played Zigeunerweisen, the composition of Sarasate. Carlson graduated from Stanford University, where she studied organizational behavior, while at Stanford, she spent a study-abroad year at Oxford University, studying the works of Virginia Woolf. In September 2011, Carlson was named to the class of the Anoka High School Hall of Fame. Carlson originally gained recognition as the co-anchor of the Saturday edition of The Early Show on CBS along with Russ Mitchell and she joined CBS News as a correspondent in 2000 and began working on The Early Show in 2002. Before her tenure at CBS, she served as an anchor and reporter for KXAS-TV in Dallas, Texas, and was an anchor and reporter at WOIO-TV in Cleveland, Ohio

13. Marysol Castro – Marysol Castro is an American broadcast journalist who was employed as a news anchor at WPIX in New York. She also was a forecaster for The Early Show on CBS in 2011. In June 2015 Castro joined New Haven-based WTNH-TV to fill in for morning traffic reports. Born on September 27,1976, to Puerto Rican parents in New York City, Castro was raised in the Bronx and attended Public School 83 and she later obtained a Master of Arts in journalism from the Columbia University Graduate School of Journalism. Prior to her career with ABC News, Castro was a general assignment reporter for WPIX in New York and she worked as a reporter for News 12, a local cable news network in the Bronx. She taught briefly at Poly Prep Country Day School in Brooklyn as an English teacher, in September 2010, Castro left GMA Weekend. On January 3,2011, as part of a complete show overhaul, on September 2,2011, it was announced that she would be leaving her post as weather anchor effective immediately. In June 2015, Castro joined WTNH-TV ABC8 in New Haven, Connecticut, to fill in as weekday morning traffic reporter, Castro was relieved of her fill-in duties in November 2015 and later left the station. In July 2015, she joined ESPN as host of Premier Boxing Champions on ESPN, marysol Castro at the Internet Movie Database

14. Julie Chen – Julie Suzanne Chen is an American television personality, news anchor, and producer for CBS. She has been the host of the U. S. version of the CBS reality-television program Big Brother since its debut in July 2000 and is the longest-serving host of any version of the show. She is also a co-host and the moderator of the CBS daytime show The Talk, previously, she was a co-anchor of The Early Show on CBS. The daughter of Chinese immigrants, Julie Chen was born in Queens, julies mother, Wan Ling Chen, married a man named Yen Chun Chen who could not be more opposite than who her father was, and the couple have been married for over 50 years. Julie has two sisters, Gladys and Victoria. Chen attended Junior High School in the Whitestone area of Queens, Chen went on to graduate from St. Francis Preparatory School in 1987. She attended the University of Southern California and graduated in 1991, majoring in broadcast journalism, the following year, while still in school, she worked for ABC NewsOne for one season as a desk assistant. She was subsequently promoted to work as a producer for the three years. The following year, she traveled to Dayton, Ohio, to work as a anchor for WDTN-TV. During her time in Dayton, Chen had plastic surgery on her eyes to make her eyes look larger. From 2002 to 2010, she was a co-host for The Early Show on CBS, before leaving the daily position, before CBS News she was a reporter and weekend anchor at WCBS-TV in New York City. Since 2000, she has also been the host of the American version of Big Brother. She has indicated in two interviews, that she takes no personal offense to the term, adding that it may derive from her precise on-air style which comes from a desire to be objective. She again acknowledged the nickname while discussing mugs made in her likeness when she proudly proclaimed, Chen is the moderator of the CBS daytime talk show The Talk, which premiered on October 18,2010. The show is similar to The View although not as politicized, the show currently features Chen, Aisha Tyler, Sharon Osbourne, show creator Sara Gilbert, and Sheryl Underwood as the co-hosts. Former co-hosts include Marissa Jaret Winokur, Leah Remini, and Holly Robinson Peete, in January 2015, Chen guest-starred in the NCIS, Los Angeles episode In The Line of Duty portraying a U. S. Ambassador. Following her graduation from USC as a broadcasting and English major, she became an assistant for ABC News in Los Angeles, California. There, she met her longtime boyfriend, television news editor Gary Donahue

15. Alexis Christoforous – Alexis Christoforous is a New York-based correspondent for CBS News specializing in business and consumer news since 2005. Her reports can also be heard on the CBS Radio Network, from 1999-2005 Christoforous was anchor and correspondent for CBS Marketwatch where she anchored the nationally syndicated program MarketWatch Weekend. She was also and continues to be an anchor for the local CBS affiliate, WCBS-TV. In addition to her business reporting, Christoforous conducts many newsmaker and entertainment interviews, including Madonna, Tom Cruise, Ringo Starr, Tony Bennett and her father is Greek-Cypriot and her mother is Italian-American. Christoforous graduated cum laude from New York University with a degree in English and she lives in New York City with her husband and three children. Christoforous covered the stock market bull run of the early 1990s, official CBS News Bio CBS News Home, Click on Moneywatch to see Alexis daily reports NEW. Moneywatch. com additional videos WCBS TV News CBS Early Show - Morning News CBS News Sunday Morning CBS Newspath CBS Moneywatch

16. Connie Chung – Constance Yu-Hwa Chung Povich, known as Connie Chung, is an American journalist. She has been an anchor and reporter for the U. S. television news networks NBC, CBS, ABC, CNN, some of her more famous interview subjects include Claus von Bülow and U. S. Representative Gary Condit, whom Chung interviewed first after the Chandra Levy disappearance, in 1993, she became only the second female to co-anchor a network newscast as part of CBS Evening News. She is married to show host Maury Povich and they have one adopted son. The youngest of five children, Chung was born and raised in Washington and her father, William Ling Chung, was an intelligence officer in the Chinese Nationalist Government. She graduated from Montgomery Blair High School in Silver Spring, Maryland and went on to receive a degree in journalism at the University of Maryland and she has been married to talk show host Maury Povich since 1984. Chung converted to Judaism upon marrying Povich, Chung has since become devoted to the faith, and attends synagogue with her family. Chung has noted publicly that she and Povich maintain a kosher lifestyle year round, Chung announced that she was reducing her workload in 1991 in the hopes of getting pregnant. Together, they have one son, Matthew, whom they adopted on June 20,1995, Chung was a Washington-based correspondent for the CBS Evening News with Walter Cronkite in the early 1970s, during the Watergate political scandal. Later, Chung left to anchor evening newscasts for KNXT, the owned and operated station in Los Angeles. Chung also anchored the primetime news updates for West Coast stations from the KNXT studios at Columbia Square during her tenure there. In 1983 Chung returned to network news as anchor of NBCs new early program, NBC News at Sunrise and she was also anchor of the Saturday edition of NBC Nightly News starting in 1983. NBC also created American Almanac and 1986, which she co-hosted with Roger Mudd, in 1989, Chung left NBC for CBS where she hosted Saturday Night with Connie Chung, and anchored the CBS Sunday Evening News. On June 1,1993, she became the woman to co-anchor a major networks national news weekday broadcast. While hosting the CBS Evening News, Chung also hosted a side project on CBS, after her unsuccessful co-anchoring stint with Dan Rather ended in 1995, Chung left CBS. She eventually jumped to ABC News where she co-hosted the Monday edition of 20/20 with Charles Gibson and began independent interviews, a field which would soon become her trademark. Chung asked Mrs. Gingrich to just whisper it to me, many people interpreted Chungs suggestion that if Mrs. Gingrich would whisper this statement it would be promised that the statement would be off the record. Bill Carter for the New York Times reported, Ms, the interview was also parodied on Saturday Night Live

17. Charles Collingwood (journalist) – Charles Collingwood was an American journalist and war correspondent. He was an member of Edward R. Murrows group of reporters known as Murrows Boys. He was also among the ranks of television journalists that included Walter Cronkite, Eric Sevareid. Collingwood was born in Three Rivers, Michigan, and graduated from Deep Springs College, in 1939 he received a Rhodes Scholarship to study at Oxford University. He covered World War II for United Press in London, and was recruited to CBS by Edward R. Murrow. He established himself as an urbane and spontaneously eloquent on-air journalist, in 1942 Collingwood was sent to cover the North African Campaign, where he proved his reporting abilities despite being considered green as a broadcast journalist. On D-Day he landed at Utah Beach hours after the first wave of soldiers hit the beaches, of the CBS reporters accompanying the ground invasion, he recorded a report on June 6 that made it to broadcast two days later. The other CBS correspondents on the ground, Bill Downs and Larry LeSueur, were not able to deliver reports until days later because of trouble setting up mobile transmitters. The recording bore a label said to hold it back until Paris was actually liberated, but the technician at CBS did not read the label. Paris was actually liberated three days later on August 25, after World War II Collingwood remained with CBS and established himself as a television journalist. One of his first roles on television was as host of the CBS documentary series Adventure and he went on to become chief correspondent of CBS and host of its Eyewitness to History series. He was a figure in CBS expansion to include international coverage. Collingwood accompanied the First Lady of the United States, Jacqueline Kennedy on a tour of the White House that she had renovated during the first year of her husbands presidency. The resultant film, A Tour of the White House with Mrs. John F. Kennedy, was broadcast on Valentines Day in 1962, the program was seen by 80 million viewers and broadcast in 50 countries including Russia and China. In the late 1960s, Collingwood was the first U. S. reporter allowed into North Vietnam, the visit was largely the inspiration for Collingwoods 1970 espionage novel, The Defector. The book received praise for its merits as a thriller. He later covered the White House and numerous other sites and he was married to actress Louise Allbritton from 1946 until her death from cancer in 1979. He later married the Swedish singer Tatiana Angelini-Jolin and remained married to her until his death and he died from cancer on October 3,1985 at Lenox Hill Hospital in New York City

18. Nancy Cordes – Nancy Cordes is the CBS News congressional correspondent, based in Washington, D. C. She is a contributor to all CBS News programs and platforms. Born Nancy Weiner in Los Angeles, Cordes grew up in Hawaii on the islands of Kauai and she is a graduate of Punahou School in Honolulu and a Phi Beta Kappa and magna cum laude graduate of the University of Pennsylvania in 1995. Cordes received a degree in public policy at Princeton Universitys Woodrow Wilson School of Public. Before that, she was a Washington-based correspondent for NewsOne, the news service of ABC News. She began her career as a reporter for KHNL-TV in Honolulu and she currently resides in Washington, DC, with her husband, daughter, and son

19. Katie Couric – Katherine Anne Katie Couric is an American journalist and author. Couric has been a television host on all Big Three television networks in the United States and she worked for NBC News from 1989 to 2006, CBS News from 2006 to 2011, and ABC News from 2011 to 2014. In addition to her television roles, she hosted Katie. Some of her most important notable roles include co-host of Today, anchor of the CBS Evening News and she also reported for nearly every television news broadcast across ABC, CBS and NBC. Courics first book, The Best Advice I Ever Got, Lessons from Extraordinary Lives, was a New York Times best-seller, in 2004, Couric earned induction into the Television Hall of Fame. C. Although her mother was Jewish, Couric was raised as a Presbyterian, in a report for Today, she traced her patrilineal ancestry back to a French orphan who immigrated to the U. S. in the 19th century and became a broker in the cotton business. Couric attended Arlington Public Schools, Jamestown Elementary, Williamsburg Middle School, as a high school student, she was an intern at Washington, D. C. all-news radio station WAVA. She enrolled at her fathers alma mater, the University of Virginia, Couric served in several positions at UVAs award-winning daily newspaper, The Cavalier Daily. During her fourth year at UVA, Couric was chosen to live as Senior Resident of The Lawn and she graduated in 1979 with a bachelors degree in American Studies. Courics first job in 1979 was at the ABC News bureau in Washington, between 1984 and 1986, she worked as a general-assignment reporter for the then-CBS affiliate WTVJ in Miami, Florida. During the following two years, she reported for WRC-TV, the NBC owned- and -operated station in Washington, D. C. work which earned her an Associated Press award, Couric joined NBC News in 1989 as Deputy Pentagon Correspondent. From 1989 to 1991, Couric was an anchor substitute and she also subbed for Daniels, Norville, and John Palmer as the news anchor on Today. In 1989, Couric joined Today as national political correspondent, becoming a substitute co-host in February 1991 when Norville had to leave, Norville did not return and Couric became permanent co-anchor on April 5,1991. While at NBC, Katie Couric occasionally filled in for Tom Brokaw on NBC Nightly News, from 1989–1993, Couric also filled in for Maria Shriver on the Sunday Edition of NBC Nightly News and for Garrick Utley on the Saturday Edition of NBC Nightly News. In addition, during her time on Today she served as a host of the annual Macys Thanksgiving Day Parade for 15 years from 1991-2005, Couric hosted or worked on a number of news specials, like Everybodys Business, Americas Children in 1995. Similar entertainment specials were Legend to Legend Night, A Celebrity Cavalcade in 1993, Couric has also co-hosted the opening ceremonies of the Olympic Games. She has broadcast with Bob Costas, beginning with the 2000 Summer Olympics, John F. Kennedy, Jr. gave Couric his first and last interviews. Couric has won multiple television reporting awards through her career, including the prestigious Peabody Award for her series Confronting Colon Cancer, Couric has also interviewed former British Prime Minister Tony Blair, U. S. Secretary of State Hillary Rodham Clinton, Harry Potter author J. K

20. Lee Cowan – Leland P. Lee Cowan is the CBS News National Correspondent for the CBS Evening News and substitute anchor for CBS Sunday Morning. Leland P Lee Cowan was born in Salt Lake City, Utah, Cowan, a surgical and radiation oncologist, and Constance W. Cowan. He is a 1988 graduate of the University of Washington and he is married to Molly Palmer, a television associate producer and daughter of television news correspondent John Palmer and writer Nancy Doyle Palmer. Cowan was a frequent correspondent for NBC Nightly News with Brian Williams, prior to joining NBC News, he was a reporter for CBS News in the CBS NEWSPATH division. He previously worked for NBC affiliate WLWT in Cincinnati, CBS affiliate WWMT in Kalamazoo, Michigan and KCOY in Santa Maria, California, in addition to KIEM in Eureka, California

21. Jan Crawford – Jan Crawford is a television journalist, author, and lawyer. She currently serves as both the political correspondent and chief correspondent for CBS News and previously for ABC News. She appears regularly on the CBS Evening News, Face the Nation, CBS This Morning and she led CBS Newss coverage of the 2012 Presidential Elections. Crawford grew up on a farm in rural Alabama, graduating from Albert P. Brewer High School, then graduated from the University of Alabama in 1987 and she joined the Chicago Tribune as a reporter in 1987. After graduating from law school, she began covering legal affairs for the Tribune, in 1996, she won the Tribunes top reporting award for her work in a 13-part series on the South a generation after the civil rights movement. In 2001, her work was honored with the Tribunes top reporting award, in his first television interview, Chief Justice Roberts talked to Crawford about the court, his views on the law, and his life since taking office. Ford, on the occasion of Fords funeral, from 1998 until 2007, Crawford provided legal analysis on the Supreme Court for The NewsHour with Jim Lehrer. From 2007 to 2009, she had been senior legal correspondent for ABC, in 2010, she began work for CBS, with a blog called Crossroads. Currently she is the legal and political correspondent for CBS. Crawford has taught journalism at American University and frequently speaks about the court to universities, law schools, legal organizations and civic groups across the country. Jan Crawford Greenburg, Supreme Conflict, The Inside Story of the Struggle for Control of the United States Supreme Court New York, Penguin Press,2007. tv

22. Walter Cronkite – Walter Leland Cronkite, Jr. was an American broadcast journalist, best known as anchorman for the CBS Evening News for 19 years. During the heyday of CBS News in the 1960s and 1970s, Kennedy, civil rights pioneer Martin Luther King, Jr. and Beatles musician John Lennon. He was also known for his coverage of the U. S. space program. He was the only recipient of a Moon-rock award. Cronkite is well known for his departing catchphrase And thats the way it is, Walter Leland Cronkite, Jr. was born on November 4,1916, in Saint Joseph, Missouri, the son of Helen Lena, and Dr. Walter Leland Cronkite, a dentist. He had remote Dutch ancestry on his fathers side, the family surname originally being Krankheyt, Cronkite lived in Kansas City, Missouri, until he was ten, when his family moved to Houston, Texas. He was a member of the Boy Scouts and he attended college at the University of Texas at Austin, entering in the Fall term of 1933, where he worked on the Daily Texan and became a member of the Nu chapter of the Chi Phi Fraternity. He also was a member of the Houston chapter of DeMolay, while attending UT, Cronkite had his first taste of performance, appearing in a play with fellow student Eli Wallach. He dropped out in 1935, not returning for the Fall term and he dropped out of college in his junior year, in the fall term of 1935, after starting a series of newspaper reporting jobs covering news and sports. He entered broadcasting as an announcer for WKY in Oklahoma City. In 1936, he met his wife, Mary Elizabeth Maxwell, while working as the sports announcer for KCMO in Kansas City. His broadcast name was Walter Wilcox and he would explain later that radio stations at the time did not want people to use their real names for fear of taking their listeners with them if they left. In Kansas City, he joined the United Press in 1937 and he became one of the top American reporters in World War II, covering battles in North Africa and Europe. With his name now established, he received a job offer from Edward R. Murrow at CBS News to join the Murrow Boys team of war correspondents, CBS offered Cronkite $125 a week along with commercial fees amounting to $25 for almost every time Cronkite reported on air. Up to that point, he had been making $57.50 per week at UP, when he informed his boss Harrison Salisbury, UP countered with a raise of $17.50 per week, Hugh Baillie also offered him an extra $20 per week to stay. Cronkite ultimately accepted the UP offer, a move which angered Murrow and he also landed in a glider with the 101st Airborne in Operation Market Garden and covered the Battle of the Bulge. After the war, he covered the Nuremberg trials and served as the United Press main reporter in Moscow from 1946 to 1948, in 1950, Cronkite joined CBS News in its young and growing television division, again recruited by Murrow. Cronkite began working at WTOP-TV, the CBS affiliate in Washington and he originally served as anchor of the networks 15-minute late-Sunday-evening newscast Up To the Minute, which followed Whats My Line. at 11,00 pm ET from 1951 through 1962

23. John Charles Daly – The second of two brothers, Daly was born in Johannesburg, South Africa, where his American father worked as a geologist. After his father died of a fever, Dalys mother moved the family to Boston. He attended the Tilton School and later served on its board of directors for many years and he did his post-secondary education at a junior college and then finished his studies graduating from Boston College. Daly worked for a time in a factory and for a transit company in Washington before becoming a reporter for NBC Radio. Daly began his career as a reporter for NBC Radio, and then for WJSV. Through covering the Roosevelt White House, Daly became known to the national CBS audience as the announcer for many of the Presidents speeches. In late 1941, Daly transferred to New York City, where he became anchor of The World Today, during World War II, he covered the news from London as well as the North African and Italian fronts. Daly was a war correspondent in 1943 in Italy during Gen. George S. Pattons infamous slapping incidents. After the war, he was a reporter on CBS Radios news/entertainment program CBS Is There. As a reporter for the CBS radio network, Daly was the voice of two historic announcements, transcriptions of those bulletins have been preserved on historical record album retrospectives and radio and television documentaries. Dalys first foray into television was as a panelist on the game show Celebrity Time and this led to a job in 1950 as the host and moderator on a new panel show produced by Goodson–Todman, Whats My Line. The show lasted 17 years with Daly hosting all but four episodes of the weekly series, in 1954–55, in addition to his duties with Whats My Line. Daly also hosted the year of the NBC Television game show Who Said That. in which celebrities tried to determine the speaker of quotations taken from recent news reports. Each panelist introduced the next in line at the start of the show, upon Fred Allens death in 1956, Random House co-founder and humorist Bennett Cerf became the anchor panelist who would usually, but not always, introduce Daly. Cerf usually prefaced his introduction with a pun or joke that over time became a pun or joke at Dalys expense, Daly would then often fire back his own retort. Cerf and Daly enjoyed a friendly feud from across the stage for the remainder of the history of the program, the mystery guest on the final CBS program was Daly himself. According to producer Gil Fates, Daly was resistant to changes that would have appealed to a younger audience, for example, Daly usually referred to the panelists formally, e. g. as Mr. Cerf. The producers, Fates said, were unable to challenge Daly for fear of losing him as the shows moderator, the series spawned a brief radio version in 1952 that was also hosted by Daly

24. Elmer Davis – Elmer Davis was a news reporter, author, the Director of the United States Office of War Information during World War II and a Peabody Award recipient. Davis was born in Aurora, Indiana, the son of a cashier for the First National Bank of Aurora, one of his first professional writing jobs was with the Indianapolis Star, a position he held while attending Franklin College. A brilliant student, Davis received a Rhodes Scholarship to Queens College and his stay in England was cut short when his father fell ill and eventually died. Davis met his wife, Florence, in England, upon his return to America, Davis became an editor for the pulp magazine Adventure, leaving after a year to work as a reporter and editorial writer for The New York Times. For the next decade, Davis reported on stories ranging from pugilist Jack Dempsey to evangelist Billy Sunday and it was his coverage of Billy Sunday that gained him notoriety. Davis later left The New York Times and became a freelance writer, Davis best-known work is his company history History of the New York Times. In 1928 Davis published his one and only novel Giant Killer, a retelling of the Biblical story of David. In August 1939, Paul White, the chief at CBS, asked Davis to fill in as a news analyst for H. V. Kaltenborn. Edward R. Murrow later commented that one reason he believed that Davis was likeable was his Hoosier accent, by 1941, the audience for Davis nightly five-minute newscast and comment was 12.5 million. On June 1,1941, Colgate-Palmolive-Peet began sponsoring seven-days-a-week newscasts by Davis on CBS, the program was carried on 95 stations from 8,55 to 9 p. m. Eastern Time. Davis spent two and a half years reporting the news on radio and gaining the trust of the nation, even though Davis was being paid $53,000 per year from CBS, he left the network to work in government during the crisis of World War II. He argued that Japanese propaganda proclaiming it a war could be combated by deeds that counteracted this. Davis has been termed one of the forefathers of the 442nd Regimental Combat Team. Davis was also instrumental in loosening censorship rules that forbade the publication of images of dead GIs on the battlefield, the government also restricted what reporters could write, and coverage was generally upbeat and bloodless. Davis believed that the American public had a right to be informed about the war within the dictates of military security. Censorship was loosened, but the media was forbidden from showing the faces of the dead or the insignia of the units they belonged to. Following the war, Davis continued his career in radio, using the platform to criticize Senator Joseph McCarthy for his anti-communist investigations and he was a longstanding member of The Baker Street Irregulars, the literary society dedicated to keeping green the memory of Sherlock Holmes. Davis retired from broadcasting in 1953 after suffering a heart attack and he died in May 1958 of complications from a stroke

25. John Dickerson (journalist) – John Frederick Dickerson is an American journalist. Dickerson is the host of Face the Nation on CBS News, the director of CBS News, Chief Washington Correspondent for CBS News. Before hosting Face the Nation, he was the longtime Chief Political Correspondent at Slate, before joining Slate, Dickerson covered politics at Time magazine for 12 years, serving the last four years as their White House correspondent. Dickerson is a son of C. Wyatt Dickerson and Nancy Dickerson Whitehead and he has three sisters and one brother. He grew up in McLean, Virginia at Merrywood, a Georgian-style mansion high on a bluff overlooking the Potomac River. Dickerson graduated from Sidwell Friends School in 1987 and holds a degree in English with Distinction from the University of Virginia. On Her Trail, Dickersons book about his relationship with his late mother Nancy Dickerson Whitehead, in a Washington Post review, staff writer Elsa Walsh called the book riveting. Before joining Slate, Dickerson covered politics at Time magazine for 12 years, Dickerson hosted Face the Nation three times in 2009 and was appointed Political Director of CBS News in November 2011. He appeared each Wednesday on The Al Franken Show on Air America Radio, until the show ended in 2007 and he appears on PBSs Washington Week and the Slate Political Gabfest, a weekly podcast with David Plotz and Emily Bazelon. Dickerson is also the host of Whistlestop, a Slate podcast about presidential history, Dickerson took over as host of Face the Nation on June 7,2015. He is the author most recently of the book, Whistlestop, My Favorite Stories from Presidential Campaign History published by Twelve, Dickerson co-wrote a July 17,2003, Time article, A War on Wilson. Which attributed the leak of Valerie Plames CIA identity to senior Bush administration officials, writing for Slate in February 2006, Dickerson speculated about why Patrick Fitzgerald never called him as a grand jury witness for his bit role in the drama. Another reporter, Tamara Lipper of Newsweek, reportedly walked away before he spoke of Plame, Dickerson has disputed Fleischers account, claiming that Fleischer urged him to look into who sent Wilson but that he did not mention Plames name or CIA identity. They suggested he was sent on his mission by a low level person at the agency, neither Lipper nor Gregory has commented publicly about what Fleischer told them. On January 31,2007, former Time reporter Matthew Cooper testified that Dickersons Africa sources contributed information to the article A War on Wilson, youve looked back before 9/11 for what mistakes might have been made. After 9/11, what would your biggest mistake be, would you say, on a conference call with Clinton staff, Dickerson asked, What foreign policy moment would you point to in Hillarys career where shes been tested by crisis. John Dickerson on Twitter Appearances on C-SPAN

26. Seth Doane – Seth Doane is an American television journalist, currently working for CBS News. Doane, the son of former Massachusetts Republican State Senator Paul Doane, was born and raised in Harwich, Massachusetts, on Cape Cod. Channel One News, the high school TV network, then made him a news anchor, sending him abroad to cover stories in San Salvador, Indonesia, Afghanistan, and the Sudan. At age twenty-two, Doane was nominated for an Emmy Award at WNYW for his School Security segment, Doane won a Peabody Award in 2004 for his series on the Sudan. In April 2006 CNN hired Doane as a video news correspondent for South Asia. He remained with CNN, based in New Delhi, until June 2007, in August 2007, Doane became a national correspondent for CBS News, covering a wide range of domestic issues. Doane is also a frequent correspondent for CBS News Sunday Morning, from April 2013 until March 2016, Doane was based in Beijing, China, covering events in Asia for CBS News. Since April 2016, he has based in Rome and covering Europe, Africa. On September 6,2014, Doane married Andrea Pastorelli in a civil ceremony in Arezzo

27. Bill Downs – William Randall Bill Downs, Jr. was an American broadcast journalist and war correspondent. He worked for CBS News from 1942 to 1962 and for ABC from 1963 until his death and he was best known for his work with Edward R. Murrow as one of the original Murrow Boys. Downs reported from both the Eastern and Western fronts during World War II, and was the first to deliver a live broadcast from Normandy to the United States after D-Day, after the surrender in Europe, he joined a press party that toured Asia prior to V-J Day. He entered Tokyo with Allied occupation forces and covered the Japanese surrender and he later covered the Bikini Atoll nuclear tests, the Berlin Blockade, and the Korean War. In the 1950s, he was an early and prominent voice urging Murrow to use his platform on See It Now to challenge Senator Joseph McCarthy, Downs was born in Kansas City, Kansas to William Randall Downs, Sr. and Katherine Lee Downs. He served as the editor of the Daily Kansan at the University of Kansas. He began his career as a reporter for the Kansas City Star. He soon joined the United Press and worked stints at the Denver, at the end of 1940 he was transferred to London, where he covered the war in Europe as a wire reporter. In September 1942, his former UP colleague Charles Collingwood introduced him to Edward R. Murrow, at the time, Murrow was in search for a reporter to relieve Larry LeSueur as CBSs Moscow correspondent. Prior to hiring Downs, Murrow had him undergo two pro forma voice tests, both of which went poorly due in part to Downs gruff voice, an issue which would affect him throughout his career. After Downs failed the tests, Murrow sent him to Piccadilly Circus. Murrow loved his account so much that he hired him on the spot, offering $70 weekly, Downs was soon sent to head CBSs Moscow bureau and remained there from December 25,1942 to January 3,1944. Throughout 1943 Downs delivered intermittent shortwave reports on CBS World News Roundup and he stayed at the Hotel Metropol in Moscow with other Western foreign correspondents along with their secretaries and translators. They faced heavy censorship by the Ministry of Foreign Affairs, which required correspondents to submit articles and this led to frequent clashes between government officials and foreign correspondents, who were prohibited from filing any reports that might reflect negatively on Moscow. Access to military updates was often limited to official communiqués and articles in government sanctioned newspapers like Pravda, up-to-date maps of the Soviet Union were hard to obtain, and reporters had trouble gathering basic information from the front lines. As the war progressed, correspondents were given access to liberated areas. They were taken to Oryol, where the Soviets had exhumed a grave of some 300 bodies. Correspondents were also shown the devastation in Rzhev soon after the occupying Nazi troops retreated in March 1943

Claudia Soler-Alfonso,1 Michael J Bennett,2 Can Ficicioglu1

1Department of Pediatrics, Section of Metabolic Disease, 2Department of Pathology and Laboratory Medicine, The Children’s Hospital of Philadelphia and Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA

Abstract: Medium-chain acyl-CoA dehydrogenase (MCAD) deficiency is the most common disorder associated with fatty acid oxidation. The disorder is characterized by inability to generate sufficient energy from fatty acid metabolism during periods of catabolic stress caused by intercurrent illness or prolonged fasting. The metabolic consequences are severe and include hypoketotic hypoglycemia leading to a Reye-like hepatic encephalopathy syndrome and sudden death. If individuals are detected before a life-threatening episode, the complications of MCAD deficiency are preventable. Newborn metabolic screening enables the early detection of MCAD deficiency in many countries worldwide. The metabolic marker for MCAD deficiency “octanoylcarnitine” (C8) can be detected with a high degree of sensitivity in the newborns by tandem mass spectrometry. The 985A>G (K329E) mutation accounts for the majority of disease alleles, and approximately 47%–80% of MCAD patients are homozygotes for this mutation. Newborns homozygous for the 985A>G mutation have higher octanoylcarnitine levels than those who are heterozygous for 985A>G mutation or possess other genotypes. Time of sampling after birth and prematurity may affect the octanoylcarnitine levels in MCAD-deficient newborns. Tandem mass spectrometry newborn blood spot screening for MCAD deficiency is accurate and effective, and reduces morbidity and mortality in affected children.

Keywords: MCAD, newborn screening, C8, octanoylcarnitine, tandem mass spectrometry, sudden death in childhood

Introduction

Mitochondrial fatty acid β-oxidation (FAO) pathway plays a key role in cellular energy production, especially during physiological response to tissue energy depletion during the periods of fasting, illnesses, and increased muscular activity. FAO provides as much as 80% of energy supply for the functioning of heart and liver at all time. The pathway is complex and includes as many as 20 individual steps (Figure 1). Within the spiral, enzymes with overlapping chain-length specificities catalyze each step.1 In the liver, the oxidation of fatty acids fuels the synthesis of ketone bodies (3-hydroxy-butyrate and acetoacetate), which are utilized as an alternative energy source by extrahepatic organs, particularly the brain.2 Inherited defects of eleven proteins directly involved in this process have been identified in humans. These include defects of the plasma membrane carnitine transporter (MIM 212140); carnitine palmitoyltransferase (CPT) I (MIM 255120) and CPT II (MIM 255110); carnitine/acylcarnitine translocase (MIM 212138); very long-chain, medium-chain, and short-chain acyl-CoA dehydrogenases (VLCAD [MIM 201475], MCAD [MIM 201450], and SCAD [MIM 201470], respectively); 2,4-dienoyl-CoA reductase (MIM 222745); long- and short-chain 3-hydroxyacyl-CoA dehydrogenases (LCHAD [MIM 143450], SCHAD [MIM 601609]); and mitochondrial trifunctional protein (MIM 600890).

Figure 1 MCAD deficiency: biochemistry and pathological consequences.
Notes: Medium-chain acyl-CoAs generated by long-chain specific enzymes at the inner mitochondrial membrane undergo a series of enzymatic steps in the matrix to generate acetyl-CoA and a chain-shortened acyl-CoA. In MCAD deficiency, this part of the pathway is blocked, leading to accumulation of medium-chain-length acyl-CoA species from which acyl-carnitines and acyl-glycines are derived.
Abbreviation: MCAD, medium-chain acyl-CoA dehydrogenase.

MCAD deficiency is the most common inborn error associated with FAO. The enzyme is responsible for catalyzing the initial step in the β-oxidation of medium-chain fatty acids (C6–C12) in the mitochondrial matrix. During prolonged fasting or illness, individuals are initially heavily dependent on energy generation from glucose oxidation until glycogen reserves are depleted. Following this depletion of glycogen reserves, glucose is generated through gluconeogenesis and then energy maintenance becomes dependent on the utilization and oxidation of fatty acids. FAO is defective in MCAD deficiency and may rapidly lead to hypoglycemia and hypoketosis when body needs FAO to produce energy. The accumulating medium-chain fatty acids such as C8 (octanoate) and other medium-chain acyl-CoAs may have toxic effects, which disrupt urea cycle and may cause hyperammonemia. Since the first patients with MCAD deficiency were described,3,4 this has become recognized as one of the most common inherited disorders of FAO seen commonly in Caucasians of northern European origin. The natural history of the disease changed since the introduction of newborn screening (NBS) technique in the early 1990s. Here, we review different aspects of this condition contrasting the evolution of natural history before and after NBS was instituted, and we describe two MCAD deficiency cases from our practice, a major metabolic reference center in the USA. These two cases exemplify the major features of this disease and the current trends of research and present-day issues related to NBS. The Children’s Hospital of Philadelphia, Committee for the Protection of Human Subjects Policies and Procedures did not require ethical approval or consent to present these cases.

Case reports

Case 1

The patient was a male infant, born at 41 weeks of gestation, and was large for gestational age (4,100 g). Prenatal history was contributory for gestational diabetes and adolescent mother. The parents were unrelated and had Caucasian origin. He was discharged on the second day of life. Next day, the infant was seen by a primary care physician and found to have poor weight gain and poor feeding since birth (13% weight loss since birth) and lethargy. The infant was referred to a small local emergency department, where he was found to be nonresponsive. Initial laboratory examination showed severe hypoglycemia and metabolic acidosis (blood glucose was 12 mg/dL, HCO3 3.5 mmol/L, pH 7.0, base excess –27 mEq). Intravenous access was very difficult to obtain. Ketones in urine were not checked. An intraosseus line was placed as an emergency and D10w was given as a bolus, which resulted in improved blood glucose level to 40 mg/dL. Subsequently, the infant was transferred to the closest neonatal intensive care unit (NICU) in their geographical area. While being transported, he developed respiratory failure and was intubated for support. The NBS laboratory called our center and reported this patient’s abnormal NBS. He had elevated C8 (octanoylcarnitine) level concerning for MCAD deficiency. NBS report was issued on the day of life three when he had the metabolic crisis. Due to snow storm in the area, the transport was not possible to our center. The infant received multiple bicarbonate boluses throughout the night, and struggled to control glycemic values that were as high as 300 through most of the night. By next morning, the infant had transaminitis (aspartate aminotransferase [AST] in the 75–150 U/L range, normal 8–40 U/L), elevated coagulation markers including partial thromboplastin time (PTT) and international normalized ratio (INR), and mild pulmonary hemorrhage. At this time, his pH was 7.2, base excess -13, and he was still comatose. He began to have seizures, which was controlled with phenobarbital. By mid-afternoon he had a fatal cardiac arrhythmia and died. Genetic testing showed homozygous 985A>G in the ACADM gene confirming the diagnosis of MCAD deficiency.

Case 2

This male infant was the product of a second uncomplicated pregnancy for an unrelated Caucasian couple. He was delivered at term by C-section due to failure to progress, and was appropriate for gestational age. Over the following 24–48 hours, he became increasingly lethargic and had difficulty in arousing. While breastfeeding on day of life two, he became apneic, limp, and pulseless. The pediatrician witnessed the event and a code was called. Infant was found to be in asystole. Chest compressions were started and he was intubated. Emergent umbilical line was placed, and he received 14 rounds of epinephrine during resuscitation. Code reportedly lasted 30 minutes. Septic work-up was initiated, and infant was transferred to an outside hospital NICU for further management. NBS report was sent at 36 hours of life, which was before he had cardiac arrest. It showed elevated levels of C8 54.52 μmol/L (cutoff <0.30 μmol/L), C10 3.91 μmol/L (cutoff <0.40 μmol/L), and C10:1 0.99 μmol/L (cutoff <0.30 μmol/L), concerning for MCAD deficiency. He was again transferred to our NICU. Acid-base status prior to the arrival from the outside hospital NICU was reported as metabolic acidosis (pH 7.2, base excess 19, lactic acid 5 mmol/L [normal <2 mmol/L). The lowest glucose level was 42 mg/dL. The blood ammonia level was 70 μmol/L. His brain MRI showed findings consistent with hypoxic ischemic encephalopathy. He was treated with D10+1/4 NS, and NaHCO3 was administered to correct acidosis. A combination of studies including organic acids, acylcarnitine profiling, and molecular analysis confirmed the diagnosis of MCAD deficiency (homozygous 985A>G). He has been treated with frequent feeding, and avoidance of fasting and supportive rehabilitation therapies after his discharge. He is now 2 months old, without new episodes of illness related to MCAD deficiency.

Clinical presentation

As we see in the two cases that we described earlier, the most common presentation of MCAD deficiency is acute encephalopathy that is frequently complicated by hypoketotic hypoglycemia. The episodes vary in severity with some individuals presenting with mild changes in mental status, described as drowsiness, that can evolve to deep coma and sudden death. These metabolic crises usually occur in the setting of metabolic stress such as intercurrent illness, more commonly gastroenteritis.

Since the first published description of MCAD deficiency in 1976, the natural history of the disease has been transformed by the implementation of NBS. This first patient presented with unexplained episodes of lethargy and unconsciousness, and typical abnormalities in urine organic acid analysis including suberylglycine and C6–C10 dicarboxylic aciduria.4 In the 1980s, further characterization of the disease improved diagnostic methods and enhanced detection of affected individuals by molecular and biochemical methods. The first report associating sudden death and MCAD deficiency appeared in 1984.5 By the early 1990s, the calculated mortality rate was 20%–30% for cases identified clinically, usually presenting with severe hypoglycemia during the first 2 years of life.6 Prior to NBS, the most common clinical presentation was acute encephalopathy. Biochemical abnormalities such as hypoglycemia were documented in 42%–96% of patients with a severe metabolic decompensation, while analysis of ketone bodies was only reported in two of those studies.4,6–10

Although not typical, the initial episode may occur in the first week of life, with symptoms ranging from hypoglycemia to coma and death.11–13 In the neonatal period, inadequate caloric intake due to difficulties with breastfeeding is considered to play a role in triggering metabolic crisis. Most patients with MCAD deficiency present after the neonatal period with the median age at the initial episode reported as 1–1.5 years.6,8 Less commonly, symptomatic adolescent and adult cases have been reported presenting with a wider variable expressivity than formerly recognized. In addition to encephalopathy, hypoglycemia, and Reye-like symptoms, manifestations in adolescents and adults include rhabdomyolysis and a more severe cardiac phenotype with cardiac arrest and arrhythmia. Approximately, 50% of the adult patients showed significant elevations in creatine kinase in the range of 3,000–4,000 U/L.14–16 Although the majority of unscreened children survived their initial episode, many children who have experienced clinically unrecognized episodes suffer from long-term complications. Prior to wide use of NBS, approximately 40% of patients with MCAD deficiency who survive after diagnosis had abnormal developmental testing, including attention deficit, speech delay, and behavioral problems.6 Santos et al reported a case of undiagnosed maternal MCAD deficiency presenting with acute liver failure during pregnancy.17 A 29-year-old Caucasian primigravida felt unwell during pregnancy and had poor oral intake. In the 39th week, blood analysis showed signs of hepatopathy, and acute fatty liver was suspected leading to Caesarean section and delivery of a healthy boy. She quickly improved after delivery. Diagnosis was made through acylcarnitine analysis that revealed abnormalities in the mother consistent with MCAD deficiency. Metabolic follow-up analyses were normal in the baby. Acute liver failure in pregnancy might have occurred coincidentally with MCAD deficiency, but it cannot be ruled out as the underlying condition triggering an unusual presentation.17

Since there are no subtle specific symptoms or signs of MCAD deficiency that could help physicians suspect this disease before patients present with severe hypoglycemic coma and its consequences, NBS for MCAD deficiency is essential to detect affected individuals.3,18–26 The introduction of tandem mass spectrometry (MS/MS) NBS programs in the 1990s have helped to reduce metabolic crisis and death in MCAD deficiency.

Previous published experience with NBS and MCAD deficiency worldwide includes England, Australia, France, the Netherlands, Denmark, Portugal, Australia, Canada, and USA, among others.7,27–36 While comparison among different programs is difficult due to different detection rates, it is clear that NBS reduces clinical manifestations and death in the MCAD-deficient population.10,36,37 It has been reported that 15%–20% of the children with MCAD deficiency died suddenly during a first episode before NBS.38–42 Since the introduction of NBS for MCAD deficiency, death caused by the defect has become rare.37 Although death is now a rare occurrence, mortality is still reported, with a general risk likely to be approximately 4%–5%.31,36 The risk appears to be more notorious in the first few days of life due to either the performance of NBS or availability of NBS results in a timely fashion,13,43 as we see in the two patients reported in this article. Although the risk of sudden death is lower in the era of NBS, there still remains a fivefold higher risk of death or a severe event in the unscreened population.44 Favorable impact of NBS for MCAD deficiency has been consistently reported by NBS programs in the USA and the rest of the world.27–32,34–36 However, long-term outcome assessments after wide use of NBS is sparse. Hsu et al reported the developmental outcomes of 32 patients with MCAD deficiency detected through New England NBS program. Only one patient, who had a history of neonatal hypoglycemia, had mild expressive speech delay. The remaining 31 patients were all developmentally normal.31 These results are congruent with findings on neuropsychological outcomes from the Australian cohort.36

Overall, discriminatory data comparing developmental outcomes in children with episodes of severe metabolic crisis versus children with appropriate intervention and early glucose administration during fasting or illness are not available. Andresen et al from the Danish cohort proposed that although follow-up information on the patients was not collected systematically, it is worth noting that at least 21% (3/14) of their not-screened patients, diagnosed after their first metabolic decompensation, suffer from long-term sequelae.27 This experience is similar to the experience published by Lindner et al from the German cohort where developmental data were available in six patients with history of metabolic decompensations. In five of these patients, the results of neurological status and IQ tests were normal on follow-up. One patient showed normal intellectual and physical development, but noted to be slightly myoclonic on neurological examination. The only patient in the German cohort who showed severe neurological and intellectual impairment (IQ 74) never experienced a metabolic decompensation. However, he presented with severe neonatal onset cardiomyopathy, which seems to be part of a syndromic condition and unrelated to MCAD deficiency.32

Investigations on suspected MCAD deficiency

Continuous vigilance and high level of suspicion for MCAD deficiency are essential, since most of the neonatal patients may present symptomatically before results of comprehensive NBS are available. MCAD deficiency should be suspected in children/adults with undiagnosed encephalopathy (mild or severe), hypoglycemia, and documented liver disease. The biochemical diagnosis is based on plasma acylcarnitine profile characterized by increased levels of hexanoylcarnitine (C6), octanoylcarnitine (C8), decanoyl and decenoylcarnitines (C10 and C10:1) species, and prominent among them being octanoylcarnitine (C8). Urine organic acids analysis shows characteristic abnormalities including the presence of hexanoyl- and suberylglycine and C6–C10 dicarboxylic aciduria. Other investigations should include frequent blood sugar monitoring, acid-base markers, ammonia level, comprehensive metabolic panel, and liver function test. Cardiac arrest could occur; an echocardiogram and electrocardiography with telemetry should be studied.45 Sudden infant deaths should always be investigated for MCAD deficiency. MCAD deficiency is estimated to be responsible for 3%–6% of sudden infant death syndrome in nonscreened populations.46 The diagnosis can be confirmed by molecular analysis of ACADM gene, which encodes for the MCAD enzyme. Determination of MCAD enzyme activity can also be done in leukocytes or lymphocytes, with an HPLC-based assay using 3-phenylpropionyl-CoA as a substrate.47,48 In families with confirmed family history of a previous child affected with MCAD deficiency, appropriate precautions should be recommended including careful monitoring of oral intake and fasting avoidance alongside with glucose monitoring within the first hours of life until NBS result is available. These families should also see a biochemical geneticist for genetic counseling and discussion of prenatal diagnosis options.

Treatment

The mainstay of treatment for MCAD is avoidance of fasting. Patients can tolerate certain hours of fasting when they are well. The maximum safe fasting time in healthy MCAD patients have been reported as up to 8 hours in infants between ages 6 and 12 months; up to 10 hours during the second year of life, and up to 12 hours after age 2 years.49 After 1 year of age, 2 g/kg of uncooked cornstarch is usually recommended as a source of complex carbohydrate at bedtime, and it provides slow release of glucose and sufficient glucose supply overnight. Blood carnitine levels may be lower than normal in MCAD patients. We recommend measuring blood carnitine levels every 6 months and supplementing carnitine (10–25 mg/kg/day), if carnitine levels are persistently lower than normal. Patients do not need any fat restriction in their diet, and breastfeeding should be allowed as long as there is sufficient breast milk.50 All patients should carry an emergency room letter, which describes urgent management. This letter should be updated and include a detailed explanation of the management of acute metabolic decompensation, emphasizing the importance of intravenous glucose regardless of “normal” laboratory results and overnight in-hospital observation when oral intake is poor.

During acute decompensation (IV), glucose (a bolus of 2 mL/kg 25% dextrose) should be initiated immediately to correct hypoglycemia and followed by intravenous glucose administration of 10% dextrose solution to provide glucose infusion rates between 10 and 12 mg glucose/kg/min. It is important to maintain frequent glucose monitoring in order to tailor individual glucose needs. If indicated, higher dextrose concentrations should be used via central line access.51 During acute illnesses including acute gastroenteritis and vomiting, intravenous fluid (IVF) with 10% dextrose should be started as early as possible, before the onset of hypoglycemia.6,9,49,52,53 Early institution of treatment with intravenous dextrose appears to be remarkably effective in reducing morbidity and mortality.9,10 MCAD patients should never receive intravenous lipid solution when they are sick and need total parenteral nutrition.

Molecular aspects

MCAD deficiency is an autosomal recessive disorder caused by mutations in the ACADM gene on chromosome 1p31.54ACADM gene consists of 12 exons that encode 421 amino acids.55 The use of NBS for early detection of MCAD deficiency has revealed a more varied mutational and biochemical spectrum of MCAD deficiency than the studies done on clinically ascertained populations.56 More than 100 different mutations of all types – missense, nonsense, splicing, and small insertions/deletions – are now known in the ACADM gene and are distributed to all the exons. Gross alterations, such as deletions and insertions involving more than 10–20 nucleotides, are rare, with only a single example reported so far.57 Prior to the institution of population-based NBS programs, clinically diagnosed MCAD patients with northern European background most often carried a common single base change mutation (c.985A>G ), accounting for up to 90% of abnormal alleles. Approximately, 80% of these patients were homozygous for this mutation, and 18% were heterozygous for c.985A>G.7,58–63

In order to explore the founder effect hypothesis, Leal et al in 2014 combined genotyping and screening data from 43 publications reporting the frequency of c.985A>G spanning over 10 million individuals, and they found significant variation in the frequency of the mutation across regions supporting a reported founder effect.58 The proportion of c.985A>G homozygotes were highest in western Europe with 4.1 (95% confidence interval [CI]: 2.8–5.6) per 100,000 individuals than the New World (3.2, 95% CI: 2.0–4.7), southern (1.2, 95% CI: 0.6–2.0), and eastern European regions (0.9, 95% CI: 0.5–1.7). No cases with the common mutation were identified in Asian and Middle Eastern regions.58

Prior to NBS, the incidence of MCAD deficiency was approximately in the range 1 in 30,000 to 1 in 135,000.28,64 Population-based NBS has revealed a much higher incidence of MCAD deficiency in newborns, ranging from 1 in 10,000 to 1 in 20,000 in northern European populations.60,65 Taking all the reported cases detected by NBS in the USA from 2001 to 2010, the incidence of MCAD was 1 in 17,759.66 In Massachusetts, approximately 1 out of 15,000 infants screened was diagnosed with MCAD, almost identical to the 1:14,000 frequency of phenylketonuria.31 In Pennsylvania and Bavaria, the MCAD frequency from the introduction of NBS has been estimated to be even greater at 1:8,000 and 1:9,000, respectively.37,67 Additionally, in countries such as the USA and the UK, where people of northwestern European descent make up a significant proportion of the population, the c.985A>G carrier frequency ranges from 1:40 to 1:100, whereas the mutation is virtually absent in the people of Japan.68 Despite the absence of the c.985A>G mutation in other populations, MCAD deficiency caused by other mutations has been reported in the children of Asia and Europe, including Portugal and Denmark, among others.12,27,35,58

Newborn screening for MCAD

MCAD deficiency may be diagnosed only after the child has expired or after permanent adverse neurological damage has occurred. Prior to the wide use of NBS, more than half of all the children were diagnosed after the age of 1 year.7 The goal of NBS is to identify affected infants before they have an acute episode and implement simple interventions such as avoidance of fasting as the mainstay of treatment. The availability of simple intervention such as avoidance of fasting makes MCAD deficiency an excellent candidate for early detection by NBS programs. NBS is conceived as a public health policy, and the understanding of cost-effectiveness for each of the conditions screened becomes a critical issue. Several studies have examined the cost-effectiveness of NBS for MCAD deficiency and have demonstrated that screening helps to both improve health and save cost.69–72

In the USA, the recommendations made by the American College of Medical Genetics in 2006 provided the foundation for the screening programs of most states to include MCAD in their mandated NBS panels. Till date, MCAD screening is performed in all 50 states in the USA. NBS programs from different countries including Germany, the UK, Austria, Portugal, Denmark, and France published their NBS data on MCAD deficiency in the past years (Table 1).

Table 1 MCAD deficiency incidence and newborn screening (NBS) C8 levels in screen-positive cases
Note:aNumber reported at the time of publication, data last accessed on April 30, 2015.

While state laws dictate which conditions need to be included in the NBS panels, state laboratories must decide how to perform the screening. Screening for MCAD deficiency is universally achieved by measuring octanoylcarnitine (C8) as the primary marker using MS/MS. Several factors can influence C8 concentrations in neonates with MCAD deficiency, including timing of sample collection, feeding/fasting state, and secondary carnitine deficiency in blood. Chace et al showed that C8 levels were significantly higher in MCAD patients younger than <3 days of age compared to the ones older than 8 days.73 This shows us that if C8 levels are higher in newborns in the first days of life, probably due to the stress of birth, it goes down once they start eating and become more anabolic. In order to avoid false negative results, the screening should be performed in the first days of life. It is also known that C8 levels may be higher than cutoff values in MCAD carriers.74,75

As expanded NBS panels have been adopted on a widespread basis, screening programs have observed that a disproportionate number of false positive screens occur in premature and very low birth weight infants who are often in the NICU.76,77 For example, Hall et al from the Atlanta cohort proposed that C8/C8:1 ratio could be an effective marker to differentiate true positive cases from false positives.30 Other reports and our own unpublished data have demonstrated that newborns with higher initial C8 values were most likely to receive a diagnosis of MCAD deficiency and were also more likely to be homozygous for the common p.K324E mutation.31 Many NBS programs use acylcarnitine ratios such as C8/10 as a marker besides individual C8 levels to increase sensitivity and specificity of the NBS test. C8/C10 ratio may remain elevated in true positive MCAD deficiency cases, even after the initial C8 level decreases.31 The C8/C10 ratio may also be a useful parameter in the assessment of patients who have novel MCAD genotypes.27,35,73,78,79

Challenges after diagnosis of MCAD through NBS

Although NBS has been proven to be efficient in detecting MCAD deficiency in the neonatal period, sudden death is still reported in these populations. Feeding difficulties, insufficient breast milk, and/or increased stress during delivery may increase the risk of metabolic crisis in the first days of life, as we described in two cases mentioned earlier, before NBS is reported. Patients with MCAD deficiency are at high risk for metabolic crisis and sudden death even after diagnosis of the disease through NBS. NBS follow-up requires 1) frequent communication and collaboration between primary care providers and metabolic centers; 2) effective communication and education with specific information to the caregivers and families with respect to the potential complications and possibility of life-threatening events during episodes of acute illness and the need for prompt medical attention during illness; and 3) social support for the family when it is needed.

The distinction among subpopulations and risk for sudden death based on initial C8 levels in NBS has been explored in the past. For example, Korman et al13 reported the NBS C8 values in two siblings with MCAD deficiency; the sibling with a C8 level of 11.8 μmol/L died suddenly at 2 days of age, whereas the sibling with a C8 level of 0.55 μmol/L was asymptomatic at 6 years of age. State-based examples include the New York State experience in which infants with MCAD deficiency who had symptoms of an acute metabolic episode had NBS C8 levels ranging from 6.8 to 37.4 μmol/L.31,80 These data suggest that C8 level in the NBS specimen may be a strong indicator of risk for sudden death in MCAD deficiency and that this level might begin at 6 μmol/L.43 From the molecular perspective, at least two cases of sudden death were heterozygous for the c.985A>G mutation and one was homozygous for a novel splicing mutation.13 Accordingly, lack of homozygosity for the c.985A>G mutation does not eliminate the risk of sudden death in MCAD deficiency when the C8 level in the newborn is noticeably increased. Determination of residual MCAD enzyme activity may also help understanding ACADM variant genotypes and may contribute to risk stratification. In 2012, Touw et al examined 84 patients from 76 families. Twenty-two percent of the subjects had a variant ACADM genotype. In patients with classical ACADM genotypes, residual MCAD enzyme activity was significantly lower (median 0%, range 0%–8%) when compared to subjects with variant ACADM genotypes (range 0%–63%; four cases with 0%, remainder 20%–63%). Patients with fatal neonatal presentations before diagnosis displayed residual MCAD enzyme activities <1%. After diagnosis and initiation of treatment, residual MCAD enzyme activities <10% were associated with an increased risk of hypoglycemia and carnitine supplementation. Subjects with variant ACADM genotypes and residual MCAD enzyme activities <10% should be considered to have the same risks as patients with classical ACADM genotypes. Parental instructions and an emergency regimen should remain as principles of the treatment in any type of MCAD deficiency, as the effect of intercurrent illness on residual MCAD enzyme activity has not been completely elucidated. There are, however, arguments in favor of abandoning the general advice to avoid prolonged fasting in subjects with variant ACADM genotypes and >10% residual MCAD enzyme activity.47,48

Despite the issues during the neonatal period and childhood, future challenges are emerging with respect to the anticipation of serious episodes and deterioration of outcome in screened individuals entering adolescence and adulthood. As they appear entirely healthy, despite having a risk of disease, this risk and the need for preventative measures may be easily undervalued and forgotten by the adolescent and young adults who remain at risk for severe metabolic decompensation. Maintaining close follow-up may be achieved by increasing the frequency of clinical visits, specifically to repeat educational goals, and provide guidance by the metabolic disease team.44

Conclusion

In conclusion, NBS using MS/MS is cost-effective for early detection of MCAD deficiency. The extended use of NBS has advanced further understanding of the molecular basis and biochemical features of patients with MCAD deficiency, with a substantial reduction in mortality and morbidity. MCAD deficiency should always be included in the differential diagnosis for neonatal hypoglycemia, particularly in infants with severe metabolic acidosis, liver dysfunction, and hyperammonemia. Although NBS has proven effective particularly in the presymptomatic individuals, severe metabolic crisis and sudden death have not been entirely prevented.

Disclosure

The authors report no conflicts of interest in this work.


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