Identification of a Novel Likely Pathogenic MT-TS2 Variant in a Patient with Mitochondrial Myopathy, Retinitis Pigmentosa and Sensorineural Hearing Loss

Mitochondrial diseases are a prevalent cause of metabolic disorders arising from nuclear or mitochondrial DNA mutations. Their clinical and genetic heterogeneity highlight their diagnostic complexity.A 55-year-old male patient with Kallmann syndrome, retinitis pigmentosa and congenital sensorineural hearing loss presented with a one-year history of generalized weakness and imbalance. Examination revealed generalized muscle atrophy, hyporeflexia, and mild tetraparesis. Following an electromyography suggestive of proximal myopathy, muscle biopsy was consistent with mitochondrial myopathy. Mitochondrial respiratory chain analysis demonstrated increased activity of complex II and residual increases in complex I and cytochrome C. Full mitochondrial DNA sequencing identified a heteroplasmic MT-TS2 variant (m.12257G>A), with 15% heteroplasmy in blood and nearly 100% in muscle tissue. This variant was classified as likely pathogenic.This case illustrates a new potentially pathogenic variant in the MT-TS2 gene. Comprehensive analysis of mitochondrial DNA is essential to establish a definitive diagnosis.