POLG1 mutations manifesting as autosomal recessive axonal Charcot-Marie-Tooth disease.

Background: Although a molecular diagnosis is possible in most patients having Charcot-Marie-Tooth disease (CMT), recessively inherited and axonal neuropathies still present a diagnostic challenge.

Objective: To determine the cause of axonal CMT type 2 in 3 siblings.

Design: Case report.

Setting: Academic research.

Participants: Three siblings who subsequently developed profound cerebellar ataxia.

Main Outcome Measures: Muscle biopsy specimen molecular genetic analysis of the POLG1 (polymerase gamma-1) gene, as well as screening of control subjects for POLG1 sequence variants.

Results: Cytochrome c oxidase deficient fibers and multiple deletions of mitochondrial DNA were detected in skeletal muscle. Three compound heterozygous substitutions were detected in POLG1.

Conclusion: Even in the absence of classic features of mitochondrial disease, POLG1 should be considered in patients having axonal CMT that may be associated with tremor or ataxia.