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

Spenger, Johannes; Maier, Esther M.; Wechselberger, Katharina; Bauder, Florian; Kocher, Melanie; Sperl, Wolfgang; Preisel, Martin; Schiergens, Katharina A.; Konstantopoulou, Vassiliki; Roeschinger, Wulf; Haberle, Johannes; Schmitt-Mechelke, Thomas; Wortmann, Saskia B. and Fingerhut, Ralph (2021): Glutaric Aciduria Type I Missed by Newborn Screening: Report of Four Cases from Three Families. In: International Journal of Neonatal Screening, Vol. 7, No. 2, 32

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.

• Item Type: Journal article
• Faculties: Medicine
• Subjects: 600 Technology > 610 Medicine and health
• Language: English