An ultra-rare cause of severe hypotonia mimicking Pompe disease in an infant: RRM2B related mitochon- drial DNA depletion syndrome with a novel mutation

Abstract

Ribonucleotide-diphosphate reductase subunit M2B(RRM2B)-related mitochondrial disease is one of the ultra-rare mitochondrial depletion syndromes. A-2-months of age girl who had severe hypotonia with absent reflexes, failure to thrive, and developmental delay was hospitalized under our care. The initial diagnosis was Pompe disease with absent reflexes and increased creatine kinase level. Enzyme analysis for Pompe disease was normal and next-generation sequence panel analysis of 450 genes related to metabolic disorders revealed a novel mutation in the RRM2B gene. The patient died at the age of 2.5 months. Up to date, there have been reports of 31 patients with infantile forms of RRM2B. This patient presented with little features to suggest a mitochondrial disorder. In conclusion, RRM2B mutations should be included in the differential diagnosis of the Pompe disease in infants with severe hypotonia. This case report also expands the mutation spectrum of rare infantile form of the RRM2B mutations.