Childhood-onset type I glutaric aciduria: the impact of delayed diagnosis

*Correspondence: [e-mail].

Abstract

Case Presentation: 10-month-old infant, daughter of non-consanguineous parents, without previous comorbidities, with post-vaccination fever two months ago associated with seizures and evolving since then with motor regression characterized by difficulty in sustaining head/trunk, global hypotonia and uncoordinated involuntary movements in the limbs. Initial investigation ruled out infection, including normal CSF. Cerebral MRI showed bilateral and symmetric T2/FLAIR hypersignal, with diffusion restriction in the caudate nucleus, lentiform and cerebral peduncle. Whole-exome sequencing identified pathogenic variants (p.Arg227Pro / p.Arg402Trp) in the GCDH gene.

Discussion: Type I glutaric aciduria is a rare, autosomal recessive disease caused by glutaryl-Coa dehydrogenase deficiency by mutations in the GCDH gene, leading to increased concentrations of glutaric acid, 3-hydroxyglutaric acid, glucatonic acid and glutarylcarnitine with potential neurotoxicity. The clinical presentation is variable and may occur in the first months/years of life with episodes of acute encephalopathy (hypotonia, seizures, motor regression and dystonia) usually precipitated by some stressors. On neuroimaging, the typical finding is bilateral damage to the basal ganglia. Treatment includes a low-lysine diet, L-carnitine supplementation, and emergency treatment during catabolic episodes.

Final Comments: Type I glutaric aciduria is potentially treatable and its early diagnosis should be sought, ideally in neonatal screening tests, as the treatment aims to prevent acute encephalopathy attacks, which impact on the development of these individuals.

Publication History

Article published online:
12 May 2025