2-methylbutyryl-CoA dehydrogenase deficiency in Hmong infants identified by expanded newborn screen

In April 2000, the Wisconsin Newborn Screening Program implemented tandem mass spectrometry (MS/MS) technology to expand the newborn screening panel from 13 to 48 disorders, the majority of which are inborn errors of metabolism. Among other tests, this technology measures the acylcarnitine profile from blood spots collected from infants at 24 to 48 hours of age. During the first 5.75 years of expanded screening, 27 infants were identified with elevated C5-acylcarnitine concentrations, an unexpectedly high number for any inborn error of metabolism. For these infants, elevated C5-acylcarnitines suggested a diagnosis of isovaleric acidemia (IVA), a metabolic defect of leucine metabolism. Subsequent testing showed that the infants did not have isovaleric acidemia, but did have 2-methylbutyryl-CoA dehydrogenase deficiency or 2-MBAD deficiency, a newly described defect of isoleucine metabolism. (An official abbreviation has not been established for this disorder. Other abbreviations include SBCADD, 2-MBG, and 2-MBCD deficiency.) All but 1 of the 27 infants identified with 2-MBAD deficiency are offspring of Hmong parents. To date, those diagnosed with the disorder in the Hmong community have been largely asymptomatic, though further research is needed to determine whether newborns with 2-MBAD deficiency are at risk for neurodevelopmental disorders.