Compound Heterozygous Mutations Presented with Quadriparesis and Menopause. A Case Report

Area of Science:

• Genetics
• Cell Biology
• Neurology

Background:

• Mitochondria are crucial for cellular metabolism via respiratory complexes.
• Defects in these complexes lead to mitochondrial dysfunction and disease.
• Mutations in SLC25A10 are linked to mitochondrial DNA depletion syndrome, usually autosomal recessive.

Observation:

• An 18-year-old female presented with progressive hypotonia, quadriparesis, spasticity, and hearing loss since infancy.
• She experienced early puberty and secondary amenorrhea at age 17.
• Previous evaluations were inconclusive, prompting further investigation.

Findings:

• Whole-exome sequencing revealed compound heterozygous mutations in SLC25A10.
• Simultaneous heterozygous mutations in HFE and TTN genes were also identified.
• These genetic findings provided an explanation for the patient's complex clinical presentation.

Implications:

• This case highlights a rare autosomal recessive mitochondrial DNA depletion syndrome presentation with compound heterozygous SLC25A10 mutations.
• It underscores the diagnostic value of whole-exome sequencing in complex, undiagnosed genetic and metabolic disorders.
• The findings expand the mutational spectrum and clinical manifestations associated with SLC25A10.