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.