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Newborn baby laying in crib

How a baby with classic galactosemia was nearly missed: When the test succeeds but system fails

Newborn baby laying in crib

Run at the state-level, mandatory newborn screening (NBS) programs detect a host of hereditary disorders so that infants can be treated before further damage, or even death, occurs.

Newborn screening (NBS) programs are critical to public health. Run at the state-level, mandatory NBS programs detect a host of hereditary disorders so that infants can be treated before further damage, or even death, occurs.

While much attention is paid to testing technology, programs must still meet basic minimum requirements to reliably identify and treat all affected individuals including minimum reporting requirements, case surveillance and a dedicated short-term follow-up program. In newborn screening, success is systematic.

A new report “How a baby with classic galactosemia was nearly missed: When the test succeeds but system fails,” published in the American Journal of Medical Genetics, takes a look at an individual case that almost slipped through the cracks of a local NBS program.

One disorder detected by NBS is classic galactosemia (CG), which arises from a deficiency in the galactose-1-phosphate uridyltransferase (GALT) enzyme, leaving infants unable to metabolize galactose-1-phosophate, a monosaccharide abundantly present in milk. CG can result in fatal liver failure, sepsis and coagulopathy if the affected infant is not switched to soy-based formula within the first week of life.

CG can be detected through a combination of enzyme assay, DNA analysis and galactose quantification. However, NBS programs differ in testing protocols for CG by state, and not all NBS programs conduct all of these tests. This is of particular relevance to the Washington, D.C., metropolitan area, a regional nexus where crossing state and district lines for medical care is common.

The report describes how a D.C.-born infant was screened for CG through all three tests. While his galactose levels were normal, his GALT was low and DNA testing revealed homozygosity for a CG mutation known as K285N. In tandem, the latter two indicators constitute a true positive result for CG, and necessitate the proper issuance of referrals, precautions and follow-up, which failed to occur in this case.

The infant breastfed and displayed notable lethargy, and parents were directed to a local emergency department in a neighboring state which does not screen for CG with DNA testing.

The providers there were unfamiliar with the DNA results, and after new labs came back normal, the NBS results were deemed as “likely falsely positive” for CG. Fortunately, a provider at the community hospital forwarded the NBS results to the Children’s National Rare Disease Institute (CNRDI). Upon review, CNRDI metabolic specialists immediately sought to rectify the situation by reaching out to the family with proper instructions and arranging a clinical evaluation, which occurred 10 days after birth.

While this case had a fortunate ending, the report highlights the potential deficiencies in NBS programs, which have historically been among America’s most successful public health initiatives. The proper and timely functioning of NBS systems is contingent upon the functioning of its constituent parts, including testing, diagnosis, follow-up, management and stakeholder education.

While test results were accurate in this case, systemic shortcomings left a patient in danger. As the authors state, “Programs must keep in mind that the true success of newborn screening extends beyond just the test itself…to improve safety and care outcomes we must focus on the system.”

A clinical report by a team of authors, mainly comprised of Children’s National clinicians, was published earlier this month in the American Journal of Medical Genetics. Authors include Sarah Viall, PPCNP, MSN, a pediatric nurse practitioner in the Rare Disease Institute; Nicholas Ah Mew, M.D., director of the Inherited Metabolic Disorders Program; and Beth A. Tarini, M.D., M.S., associate director of the Center for Translational Research.