Debate Rages Over Expansion of Newborn Genetic Screening
Science Feature -- February 2005
By Ken Ortolon
Infants born with genetic defects of metabolism may be doomed to severe illness, mental retardation, or death if those defects are not identified and treated early. Yet, there is wide variation between states in the number of such disorders for which newborn infants are screened.
Now, the American College of Medical Genetics (ACMG) and the March of Dimes are pushing to expand and standardize newborn genetic screening. But while there appears to be consensus that expanded screening is appropriate and desirable, there is controversy over which conditions should be screened.
In Texas, some stakeholders, including the Texas Medical Association, question whether a sufficient infrastructure exists to carry out the expanded screening and provide the necessary follow-up and treatment for children identified with the disorders.
"In Texas, there has been a significant concern about having appropriate infrastructure, vis-à-vis physician expertise, hospital expertise, treatment expertise, if you discover a child who has an abnormality," said Corpus Christi medical geneticist Raymond C. Lewandowski Jr., MD, "If that's nonexistent, why test?"
Body Chemistry Errors
The March of Dimes says every U.S. state and territory screens newborns for at least some genetic defects. Data from the Austin-based National Newborn Screening and Genetics Resource Center (NNSGRC) show the number of disorders tested ranges from three in South Dakota to 40 in Mississippi.
Texas requires screening of every newborn for phenylketonuria (PKU), galactosemia, congenital hypothyroidism, sickle cell disease, and congenital adrenal hyperplasia.
Inborn genetic disorders are rare. NNSGRC data show some occur in about one in 3,000 U.S. infants, while others occur in fewer than one in 340,000. But Dr. Lewandowski, who serves on TMA's Council on Scientific Affairs, says screening is important because these disorders can be "disastrous if not treated in infancy."
PKU, for example, prevents babies from being able to process phenylalanine, found in nearly all foods. The condition affects about one baby in 14,000 in the United States. Without treatment and a special diet, phenylalanine builds up in the bloodstream and causes brain damage and mental retardation.
Experts say tandem mass spectrometry can screen for hundreds of inborn genetic errors. Used in biochemistry for decades, it has recently been applied to newborn screening. But physicians, parents, and others disagree over the value of such testing. While some conditions have severe consequences if undetected and untreated, others have no cure. And, still others have no known symptoms.
TMA policy, says Houston neonatologist and TMA Board of Trustees member Michael Speer, MD, is that screening should be limited to conditions physicians can treat. However, that opinion is not universal.
"If you ask the medical community, many -- and I must admit, personally, myself -- feel that if you're going to screen for something, screen for something we can treat. Physicians want to be able to offer some positive benefit from a screening test or from a treatment. However, we're hearing that some families really want to know whether their infant has a disorder, whether it is treatable or not."
The TMA Council on Scientific Affairs is reexamining association policy, considering the physical, emotional, and financial impact on children, parents, insurers, and the medical community when days, weeks, or years of medical testing may be performed to diagnose a child.
Where's the Infrastructure?
In 2003, the Texas Department of State Health Services (DSHS) asked the legislature for funding to purchase the tandem mass spectrometry equipment and hire personnel to screen all newborns for the expanded list of genetic disorders and provide follow-up for Texas infants identified with those conditions. The legislature, however, rejected the request when some groups, including TMA, opposed it.
TMA's objection was twofold. First, it was concerned about who would pay for the new screening. In 1998, the health department instituted a fee of $13.75 per test. Dr. Lewandowski says the burden for that cost fell on physicians and hospitals. Few health plans cover newborn genetic screening.
The second concern is infrastructure. TMA and others feared Texas lacked the infrastructure to carry out the expanded screening and do the necessary follow-up to ensure that children got treatment. There also were concerns about whether Texas had the necessary specialists to treat these infants and counsel their families.
"It's not just geneticists who treat these children," he said. "It's endocrinologists, it's neurologists, it's pediatricians. We have plenty of pediatricians but not a lot with expertise in these kinds of abnormalities. And, very few centers in Texas treat inborn errors."
DSHS this year is expected to again ask lawmakers for at least $3.5 million to begin tandem mass spectrometry screening of newborns. TMA officials say they support screening expansion but still want to make sure the infrastructure concerns are addressed.
Dr. Speer says Texas needs adequate infrastructure and funding for five specific elements -- screening, follow-up, diagnosis, treatment, and management and evaluation -- if an expanded screening program is to be successful.
"It's not only the ability to do the screens," he said. "It's also the ability to integrate the follow-up, the treatment plan, the quality assurance of the entire process, and indeed the accuracy of the process as it stands."
In addition, Dr. Speer says public health officials need "workable partnerships" with patients' families, primary care and other physician groups, hospitals, governmental entities, and others to adequately cover all aspects of the newborn screening continuum of care.
Dr. Speer suggested having the NNSGRC, headed by Brad Therrell, PhD, former head of the DSHS newborn screening program, do a thorough assessment of the expanded screening program. Dr. Therrell has said NNSGRC could do that assessment and have a preliminary report upon which the legislature could base a decision on what is needed to successfully expand the newborn screening program. DSHS officials have agreed and have formally requested that assessment.
TMA Council on Scientific Affairs Chair Leonides G. Cigarroa Jr., MD, says the council will follow the results of the assessment and make a recommendation to the TMA Council on Legislation on whether to support DSHS' funding request.
Ken Ortolon can be reached by telephone at (800) 880-1300, ext. 1392, or (512) 370-1392; by fax at (512) 370-1629; or by email at Ken Ortolon.
March of Dimes Pushes for National Newborn Screening Standard
The March of Dimes has recommended that all states expand their newborn genetic screening programs to cover 30 inborn genetic errors.
Nancy S. Green, MD, medical director for the March of Dimes, told participants in a stakeholders meeting hosted by the Texas Medical Association in December that her organization will seek minimal standards at both the national and state levels for newborn genetic screening. The March of Dimes recommends that all babies be screened for the following defects:
- 3-Methylcrotonyl-CoA carboxylase deficiency (3MCC),
- 3-OH 3-CH3 glutaric aciduria (HMG),
- Argininosuccinic acidemia (ASA),
- Beta- ketothiolase deficiency (BKT),
- Biotinidase deficiency (BIOT),
- Carnitine uptake defect (CUD),
- Citrullinemia (CIT),
- Congenital adrenal hyperplasia (CAH),
- Congenital hypothyroidism (HYPOTH),
- Cystic fibrosis (CF),
- Galactosemia (GALT),
- Glucose-6-phosphate dehydrogenase deficiency (G6PD),
- Glutaric acidemia type I (GA I),
- Hb S/Beta- thalassemia (Hb S/ Th ),
- Hb S/C disease (Hb S/C),
- Hearing deficiency,
- Homocystinuria (HCY),
- Isovaleric academia (IVA),
- Long-chain L-3-OH acyl-CoA dehydrogenase deficiency (LCHAD),
- Maple syrup urine disease (MSUD),
- Medium chain acyl-CoA dehydrogenase deficiency (MCAD),
- Methylmalonic acidemia (Cbl A,B),
- Methylmalonic acidemia (mutase deficiency) (MUT),
- Multiple carboxylase deficiency (MCD),
- Phenylketonuria (PKU),
- Propionic acidemia (PROP),
- Sickle cell anemia (SCA),
- Trifunctional protein deficiency (TFP),
- Tyrosinemia type I (TYR I), and
- Very long-chain acyl-CoA dehydrogenase deficiency (VLCAD).
February 2005 Texas Medicine Contents
Texas Medicine Main Page