A second MNGIE patient without typical mitochondrial skeletal muscle involvement

Area of Science:

• Genetics
• Neurology
• Mitochondrial Biology

Background:

• Mitochondrial neurogastrointestinal encephalomyopathy (MNGIE) is an autosomal recessive disorder.
• It results from mutations in the thymidine phosphorylase (TYMP) gene.
• Clinical features include gastrointestinal dysmotility, cachexia, ptosis, ophthalmoparesis, neuropathy, and leukoencephalopathy.

Observation:

• Most MNGIE patients exhibit mitochondrial dysfunction in skeletal muscle.
• This dysfunction is evident morphologically and enzymatically, with mitochondrial DNA depletion, deletions, and mutations.
• A previously reported case and the current patient share a TYMP splice-acceptor site mutation (c. 215-1 G>C).

Findings:

• Both reported cases with the c. 215-1 G>C TYMP mutation lack skeletal muscle mitochondrial involvement.
• This observation challenges the universal association of MNGIE with muscle mitochondrial pathology.
• The findings suggest a specific genotype-phenotype correlation for this TYMP mutation.

Implications:

• This genotype-phenotype correlation refines the understanding of MNGIE.
• It may guide diagnostic approaches for patients with similar TYMP mutations.
• Further research is warranted to elucidate the mechanisms underlying this variant presentation.