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

Abstract

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 late-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. Here we present 19 year-old-adolescent male with chronic renal disease for 2 years 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 clinical examination he had features of myeloneuropathy. Laboratory evaluation showed significant elevation of blood glutaryl carnitine with very low free carnitine, while extensive white matter signal changes with diffusion restriction, subependymal nodules and involvement of internal capsule were evidenced on brain magnetic resonance imaging. Diagnosis was confirmed by clinical exome sequencing which showed a pathogenic homozygous missense mutation in exon 11 of GCDH gene (c.120 C>T, p.His403Tyr). 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.

Keywords

Glutaric aciduria type-1 / GCDH gene / Myeloneuropathy / India

List of abbreviations

GA-1 - Glutaric aciduria type-1, OADs - Organic acidurias, MRC - Medical Research Council, ACMG - American College of Medical Genetics, FTH - Frontotemporal hypoplasia, C5DC - glutarylcarnitine.

Ethics approval and consent to participate

This study was performed in line with the principles of the Declaration of Helsinki. Approval was granted by the Institutional Ethics Committee of National Institute of Mental Health and Neuro Sciences (NIMHANS), Bengaluru, India (Date: 8/8/22, No: NIMH/DO/(BS&NS)2022). Informed consent was obtained from patient and his parents.

Authors’ Contributions

All authors contributed to the study conception and design. Material preparation, data collection and analysis were performed by DB, GA, DDSA, AM, TAS, KP, BSS, TJ, SBS, SN, PR, RMC, RY, RC, SV, AN. The first draft of the manuscript was written by DB and all authors commented on previous versions of the manuscript. All authors have read and approved the final manuscript.

Funding

The authors declare that no funds, grants, or other support were received during the preparation of this manuscript.

Data availability

Data is available on reasonable request from the corresponding author.

Declaration of Competing Interest

The authors have no relevant financial or non-financial interests to disclose.

Acknowledgements

None.

Consent for publication

The authors also affirm that patient and his parents provided informed consent for publication of the images in Fig. 1.

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