A novel XPNPEP3 gene variant manifesting as rhabdomyolysis and exercise intolerance.

Biallelic mutations in XPNPEP3 gene, encoding a mitochondrial peptidase, mainly cause nephronophthisis, but associated muscle involvement remains poorly described. We report here a 44-year-old male presenting since childhood with exercise intolerance and recurrent rhabdomyolysis. Electroneuromyography revealed a sensory axonal neuropathy and brain MRI showed white matter lesions in the posterior cranial fossa. Muscle biopsy revealed ragged-red fibers, COX negative fibers and abnormal mitochondria in electron microscopy. Whole genome sequencing identified a homozygous frameshift variant in the XPNPEP3 gene. Our results expand the spectrum associated with XPNPEP3 variants, including metabolic myopathy with subclinical central and peripheral nervous system involvement.