Glutaric Aciduria Type I Missed by Newborn Screening: Report of Four Cases from Three Families

Abstract

by Johannes Spenger,Esther M. Maier,Katharina Wechselberger,Florian Bauder,Melanie Kocher,Wolfgang Sperl,Martin Preisel,Katharina A. Schiergens,Vassiliki Konstantopoulou,Wulf Röschinger,Johannes Häberle,Thomas Schmitt-Mechelke,Saskia B. Wortmann andRalph Fingerhut
Int. J. Neonatal Screen. 2021, 7(2), 32; https://doi.org/10.3390/ijns7020032 - 10 Jan 2022
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Abstract
Glutaric aciduria type I (GA-1) is a rare autosomal-recessive disorder of the degradation of the amino acids lysine and tryptophan caused by mutations of the GCDH gene encoding glutaryl-CoA-dehydrogenase. Newborn screening (NBS) for this condition is based on elevated levels of glutarylcarnitine (C5DC) in dried blood spots (DBS). Here we report four cases from three families in whom a correctly performed NBS did not detect the condition. Glutarylcarnitine concentrations were either normal (slightly below) or slightly above the cut-off. Ratios to other acylcarnitines were also not persistently elevated. Therefore, three cases were defined as screen negative, and one case was defined as normal, after a normal control DBS sample. One patient was diagnosed after an acute encephalopathic crisis, and the other three patients had an insidious onset of the disease. GA-1 was genetically confirmed in all cases. Despite extensive efforts to increase sensitivity and specificity of NBS for GA-1, by adjusting cut-offs and introducing various ratios, the biological diversity still leads to false-negative NBS results for GA-1. Full article
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