A Novel SUCLA2 Mutation Presenting as a Complex Childhood Movement Disorder

Area of Science:

• Biochemistry
• Genetics
• Neurology

Background:

• Succinate-CoA ligase (SUCLA2) deficiency is linked to mitochondrial DNA (mtDNA) depletion, causing hypotonia, dystonia, and deafness.
• Mitochondrial disorders often present with complex neurological symptoms and muscle involvement.

Observation:

• A 9-year-old boy with consanguineous parents exhibited psychomotor delay, deafness, myopathy, ataxia, and chorea.
• Normal brain MRI contrasted with lactate peaks on 1H-MRS, suggesting cerebral mitochondrial dysfunction.
• Muscle and fibroblast analysis revealed reduced activity of mtDNA-encoded respiratory chain enzymes and mtDNA depletion.

Findings:

• A novel homozygous mutation in the SUCLA2 gene, specifically within the ligase coenzyme A (CoA) domain, was identified.
• Progressive neurological symptoms and myopathy were observed in the absence of overt brain lesions on MRI.
• High-dose Coenzyme Q10 (CoQ10) therapy led to improved muscle strength and disease stabilization.

Implications:

• Screening for mitochondrial dysfunction is crucial in patients with unexplained movement disorders, even with normal brain MRI.
• Investigating potential secondary CoQ10 deficiency is important for patients diagnosed with SUCLA2 mutations.
• This case highlights a novel mutation in SUCLA2 and suggests a therapeutic role for CoQ10 in related mitochondrial diseases.