Acute myeloneuropathy due to Glutaric aciduria-1: expanding the phenotypic spectrum.

Abstract

Abstract Background: Glutaric aciduria type-1 (GA-1) is a rare metabolic disorder due to mutation in GCDH gene resulting in varied clinical manifestations. Here we report a case of adult-onset GA-1 with acute myelo-neuropathy and chronic renal failure. Institutional ethics committee approval was obtained and genetic analysis was done by clinical exome sequencing. Case presentation: A 19 year-old-man with 2 years history of chronic renal disease presented with 5 months history of sudden onset weakness of proximal and distal lower limbs and bladder retention. This was preceded by recurrent episodes of vomiting. On examination he had features of myeloneuropathy. Evaluation showed significant elevation of blood glutaryl carnitine with very low free carnitine along with brain MRI showing extensive white matter signal changes with diffusion restriction, subependymal nodules and involvement of internal capsule. Diagnosis was confirmed by clinical exome sequencing which showed a novel pathogenic homozygous missense mutation in exon 11 of GCDH gene (c.120C>T, p.His403Tyr). Conclusions: This report expands phenotypic spectrum of GA-1 to include late onset acute myelo-neuropathy with chronic renal failure. A high index of suspicion is required since early treatment might decelerate further disease progression.