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

• Main Authors: Johannes Spenger (Author), Esther M. Maier (Author), Katharina Wechselberger (Author), Florian Bauder (Author), Melanie Kocher (Author), Wolfgang Sperl (Author), Martin Preisel (Author), Katharina A. Schiergens (Author), Vassiliki Konstantopoulou (Author), Wulf Röschinger (Author), Johannes Häberle (Author), Thomas Schmitt-Mechelke (Author), Saskia B. Wortmann (Author), Ralph Fingerhut (Author)
• Format: Book
• Published: MDPI AG, 2021-06-01T00:00:00Z.
• Subjects: article
• Online Access: Connect to this object online.

Summary

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 <i>GCDH</i> 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 Description

10.3390/ijns7020032
2409-515X