Newborn screening for dihydrolipoamide dehydrogenase deficiency: Citrulline as a useful analyte
نویسندگان
چکیده
Dihydrolipoamide dehydrogenase deficiency, also known as maple syrup urine disease (MSUD) type III, is caused by the deficiency of the E3 subunit of branched chain alpha-ketoacid dehydrogenase (BCKDH), α-ketoglutarate dehydrogenase (αKGDH), and pyruvate dehydrogenase (PDH). DLD deficiency variably presents with either a severe neonatal encephalopathic phenotype or a primarily hepatic phenotype. As a variant form of MSUD, it is considered a core condition recommended for newborn screening. The detection of variant MSUD forms has proven difficult in the past with no asymptomatic DLD deficiency patients identified by current newborn screening strategies. Citrulline has recently been identified as an elevated dried blood spot (DBS) metabolite in symptomatic patients affected with DLD deficiency. Here we report the retrospective DBS analysis and second-tier allo-isoleucine testing of 2 DLD deficiency patients. We show that an elevated citrulline and an elevated allo-isoleucine on second-tier testing can be used to successfully detect DLD deficiency. We additionally recommend that DLD deficiency be included in the "citrullinemia/elevated citrulline" ACMG Act Sheet and Algorithm.
منابع مشابه
Feature construction can improve diagnostic criteria for high-dimensional metabolic data in newborn screening for medium-chain acyl-CoA dehydrogenase deficiency.
BACKGROUND In newborn screening with tandem mass spectrometry, multiple intermediary metabolites are quantified in a single analytical run for the diagnosis of fatty-acid oxidation disorders, organic acidurias, and aminoacidurias. Published diagnostic criteria for these disorders normally incorporate a primary metabolic marker combined with secondary markers, often analyte ratios, for which the...
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Citrullinemia is the earliest identifiable biochemical abnormality in 13 neonates with intrahepatic cholestasis due to a citrin deficiency (NICCD) and it has 14 been included in newborn screening panels using tandem mass spectrometry. 15 However, only one neonate was positive among 600,000 infants born in Sapporo 16 city and Hokkaido, Japan between 2006 and 2017. We investigated 12 neonates wit...
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Medium chain acyl-CoA dehydrogenase (MCAD) deficiency is a fatty acid oxidation disorder included on newborn screening (NBS) panels in many regions that have expanded to using tandem mass spectrometry for acylcarnitine screening. False positive (FP) screening results for MCAD deficiency have previously been linked to very low birth weight (VLBW) infants and those who are heterozygous for the co...
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OBJECTIVE To evaluate newborn screening by tandem mass spectrometry for detection of medium chain acyl-CoA dehydrogenase (MCAD) deficiency, a fatty acid oxidation disorder with significant mortality in undiagnosed patients. DESIGN The following were studied: (a) 13 clinically detected MCAD deficient subjects, most homozygous for the common A985G mutation, whose newborn screening sample was av...
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