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Jana and Stephen Monaco

Prenatal screening: the story of two siblings

Alex and Stephen Monaco

Stephen Monaco with his brother before a life-changing incident in 2001.

Jana and Tom Monaco have four children and two, Stephen and Caroline, were born with isovaleric acidemia (IVA) and secondary carnitine deficiency, a rare metabolic disorder. This genetic condition prevents the body from producing enzymes to break down the amino acid leucine, found in many proteins – from nuts and beans to chicken and fish. If undetected, the condition, which affects about one in 250,000 children, can be fatal. IVA can also lead to autism or severe brain damage. Fortunately, newborn screenings in every state now detect most IVA cases.

Eighteen years ago, a series of events happened with Stephen, age 3.5 at the time, which led to his diagnosis of having IVA and secondary carnitine deficiency. He celebrated his grandmother’s birthday with a family dinner on Memorial Day. The next day he woke up with symptoms of a stomach virus, which the family treated as such. The following morning he didn’t wake up at all. Jana went to his room to check on him and realized something was wrong. She called an ambulance and within 24 hours Stephen fell into a coma in her arms. He was immediately put on life support at a Virginia hospital.

Amy Lewanda, M.D., a geneticist, and Craig Futterman, M.D., an intensivist, both of whom now work at Children’s National Health System, delivered news about the condition: IVA is an inability for the IVD gene to create enzymes to break down protein. Within a 24- to 48-hour period, Stephen’s body flooded with isovaleric acid it couldn’t break down. Once the acid reached his brain he was paralyzed. Jana mentions you could find him in the emergency department of the hospital by following the odor: He reeked of ketones and isovaleric acid, which accumulated in his blood and body tissue. His blood glucose level was so low that he was practically in a diabetic coma.

Jana and Stephen Monaco

Jana and Stephen Monaco, at a charity golf tournament established in Stephen’s honor to raise awareness about and support for isovaleric acidemia (IVA).

If the Monaco family was able to get his blood checked locally at the hospital – which the clinicians did not yet have the ability to do because this condition is so rare – they may have been able to receive an early diagnosis, enabling them to intervene in infancy, as they did with their youngest daughter, Caroline.

After the diagnosis, in hindsight, Jana and Tom recognized Stephen’s symptoms as a toddler: picky eating, anemia, rejection of protein-rich foods, such as favoring jelly over peanut butter on a PB&J sandwich, opting for easy carbs, since they are easier for those with IVA to process, and breastfeeding longer, since breast milk is lower in protein. He had a peculiar odor trailing from his diaper, a common symptom of this condition. They also remembered he had a harder time recovering from a stomach virus, which left him weak and floppy, compared to one of his brothers, who had the same flu but bounced back faster. As parents, they did everything they could to promote healthy growth and development for their children – from properly installing  car seats to staying up-to-date on vaccines and enrolling everyone in activities, like Little League. They only wished they could have detected this condition earlier.

A second chance arrived six months after Stephen was diagnosed with IVA: Jana and Tom learned they were pregnant with Caroline. From studying Stephen’s condition, they knew Caroline had a 25 percent chance of having IVA and secondary carnitine deficiency. (Jana and Tom are recessive carriers for a mutated IVD gene, but remain asymptomatic.) They scheduled an amniocentesis, a prenatal test that provides information about a baby’s health from sample amniotic fluid, which can diagnose genetic defects and fetal infections. Caroline was just 16 weeks in utero, but abnormal metabolites from the amniotic fluid sample confirmed she had IVA and secondary carnitine deficiency.

Caroline Monaco

Caroline, a healthy teenager with IVA, is an example of the benefits of newborn screenings and early-life medical interventions.

Having advance knowledge about the condition enabled doctors and geneticists to create a plan for her delivery, which made a difference between her long-term prognosis and Stephen’s. After birth, she was transferred to the neonatal intensive care unit at Children’s National. She was fed a formula that prevented excess isovaleric acid build-up, part of an hour-by-hour protocol to ensure she stayed healthy. Caroline is now 16. She plays the viola in her school orchestra, rides horses and excels in school.

When Stephen was born, the state of Virginia, where the Monaco family lives, screened for eight prenatal conditions, such as PKU, a rare but more common condition. The state now screens for 31 conditions, thanks in part to Jana, Stephen and Caroline. The list grows as research evolves. Jana started advocating for these efforts in Richmond and on Capitol Hill when Caroline was 2. Her approach: Take Stephen and Caroline to her state capitol and to the U.S. Capitol to push for statewide newborn screenings – visually showing the same condition, but with two very different outcomes. How could anyone say no?

She worked with the Virginia Genetics Advisory Council and with the Health and Human Services Secretary Advisory Committee to pass the legislation, which helped detect other organic acidemias – inherited conditions that prevent babies from breaking down amino acids found in protein, creating potentially toxic situations, similar to Stephen’s. They advocated for adding other conditions to the panel, like severe combined immunodeficiency, commonly referred to as “bubble boy” syndrome. Stephan was the only newborn screening advocate in attendance with a disability. Now all 50 states have implemented these screenings.

Attendees of the charity golf event

The Monaco family raised $100,000 for the genetics division and ongoing IVA research at Children’s National Health System.

The family isn’t done yet. On Oct. 26, Stephen will celebrate his 22nd birthday and a fifth-annual golf tournament, created in his honor, to raise awareness about and support for IVA and similar conditions. The Monaco family started this tradition in 2015 on Stephen’s 18th birthday and have raised $100,000 for the genetics division at Children’s National. They hope Stephen’s legacy will leave others with a message they keep framed in their Virginia home: Learn from yesterday, live for today and hope for tomorrow.

They educate Caroline along the way, noting the annual golf tournament and their advocacy supports ongoing IVA research and care – ensuring that she and others with these rare metabolic conditions continue to live a long, healthy life, echoing their longstanding partnership with Children’s National to help children grow up stronger.

Sarah Viall

Newborn screening leader selected to advisory committee on heritable disorders in newborns and children

Sarah Viall

Sarah Viall, PPCNP, coordinator for the Newborn Screening Program at the Children’s National Rare Disease Institute (CNRDI), has been invited to serve on the Education and Training Workgroup of the Health Resources & Services Administration’s (HRSA) Advisory Committee on Heritable Disorders in Newborns and Children (ACHDNC).

Established under the Public Health Service Act, the ACHDNC focuses on reducing morbidity and mortality in newborns and children who have, or are at risk for, genetic disorders. The Committee currently recommends that all newborn screening programs include a Uniform Screening Panel that monitors for a total of 34 core disorders and another 26 secondary disorders.

In addition to developing recommendations on national newborn screening guidelines, the ACHDNC also advises the U.S. Department of Health and Human Services Secretary on the most appropriate application of newborn screening technologies, tests, policies and standards. The Committee provides technical information that helps develop Heritable Disorders Program policies and priorities that enhance the ability of local and state health agencies to provide screening, healthcare services and counseling for newborns and children affected by genetic disease.

Viall had previously spent a year observing meetings for the ACHDNC Education and Training Workgroup.

“I am thrilled to be an official member that can contribute to the important work of educating communities about newborn screening,” says Viall.

Gerard Martin

European workgroup creates recommendations for CCHD pulse oximetry screening

Gerard Martin

Several experts, including Gerard R. Martin, M.D., recently published recommendations for the use and standardization of pulse oximetry screening for critical congenital heart defects in newborns.

The European Pulse Oximetry Screening Workgroup recently published recommendations for the use and standardization of pulse oximetry screening for critical congenital heart defects in newborns. Children’s National Medical Director of Global Services Gerard R. Martin, M.D., was among the experts that compiled the recommendations.

Approximately 1 in 500 babies is born with a critical congenital heart defect (CCHD). Because these conditions can cause serious, life-threatening symptoms, early detection and intervention is essential. Pulse oximetry screening (POS) – a method that measures oxygen saturation – is regarded as a simple, quick and reliable tool for early detection of CCHD, and was recommended for use in screening by the American Academy of Pediatrics and the American Heart Association in 2011.

In Europe, although POS is being used by an increasing number of hospitals, few countries have issued national guidelines recommending universal POS. To remedy this situation, neonatologists, experts in CCHD screening, and representatives from major scientific pediatric societies across Europe came together to create recommendations for the use and standardization of POS for early detection of CCHD across Europe.

Their recommendations, which were published in The Lancet, are as follows:

  • POS for critical congenital heart defects should be recommended for all European countries
  • POS should be done with new-generation equipment that is motion tolerant
  • Screening should occur after 6 hours of life or before discharge from the birthing centre (preferably within 24 hours after birth)
  • Screening should be done in two extremities: the right hand and either foot
  • Each country should consider the advantages and disadvantages of the two available protocols and use that which best suits their population

Lessons learned from newborn screening for critical congenital heart defects

chd_screening

What’s Known

In 2011, screening for critical congenital heart defects (CCHD) became the second point-of-care newborn screening test added to the Recommended Uniform Screening Panel, and it has since been widely adopted. Heart defects are the primary targets for CCHD screening, which often require evaluation by echocardiogram. An original list of seven conditions represented the most common critical lesions which routinely present with hypoxemia for newborns. Endorsed by the American Academy of Pediatrics and four other professional medical societies, the CCHD screening using pulse oximetry is required by law in all but two states. Remaining challenges include national data collection and outcomes analyses at the population level.

What’s New

An expert panel including Gerard R. Martin, MD, a cardiologist at the Center for Translational Science at Children’s National Health System, reviewed current practices in newborn screening for CCHD and identified opportunities for improvement. The panel’s study expanded the list of core conditions to 12 to emphasize the importance of other potentially critical, yet treatable secondary conditions. Roughly 79 percent of “positive” screens for CCHD identify secondary conditions, such as sepsis and pulmonary diseases. The study found algorithm misinterpretation was common in states collecting outcomes data, emphasizing needs for proper training and quality-assurance feedback mechanisms. Public health surveillance varied dramatically, with nearly one-fifth of states neither actively collecting data nor planning to do so. Additional CCHD screening research in special settings like the NICU, out-of hospital settings, and areas with high altitude may result in adaptations to screening protocol. Future improvements to the current screening algorithm and analyses of the impact on CCHD outcomes will rely on further investment in a national data repository.

Questions for Future Research

Q: What will be the impact on present screening for CCHD on outcomes of non-CCHD secondary conditions?
Q: What is the optimal algorithm for CCHD based on screening and testing ease of use, costs, resource utilization, and sensitivity for different treatment settings?
Q: What will be the impact on present screening for CCHD on outcomes of non-CCHD secondary conditions?

Source: Lessons Learned From Newborn Screening for Critical Congenital Heart Defects.” M.E. Oster, S.W. Aucott, J. Glidewell, J. Hackell, L. Kochilas, G.R. Martin, J. Phillippi, N.M.Pinto, A. Saarinen, M. Sontag, and A.R. Kemper. Published by Pediatrics May 2016.