Hypertrophic cardiomyopathy as a novel phenotypic feature of NSUN3-related mitochondrial disease: a case report with review of the literature

NSUN3 (biallelic variants — mitochondrial RNA methyltransferase)

Phenotypic expansion: HCM as novel manifestation of NSUN3 deficiency — defective cytosine methylation at the tRNA wobble base in mitochondria

NSUN3 encodes a mitochondrial RNA methyltransferase responsible for cytosine methylation at the tRNA wobble base, regulating mitochondrial translation. Biallelic variants impair oxidative phosphorylation. The previously described clinical picture included developmental delay, hypotonia, optic atrophy and neurological involvement — without documented cardiac involvement. The authors report severe HCM as a new clinical feature and present long-term follow-up of their case, expanding the phenotypic spectrum of NSUN3 disease.

Synthesis written by Geno'X. For the full original abstract, please refer to the source publication.

Important phenotypic expansion to integrate into patient management: propose systematic cardiac workup (ECG, echocardiography) in all NSUN3 patients, even in the absence of cardiovascular symptoms. Parallels to draw with other mitochondrial diseases where HCM is an underrecognized complication. Short but clinically actionable article.

known gene +0; biallelic AR +1; novel HCM expansion +2; long-term follow-up +1; cardiac surveillance impact +1; J Pediatr Endocrinol Metab +1