Résumé :
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Objective : to report 2 cases of isolated ataxic neuropathy with onset in adult age and associated with mitochondriopathy. Background : Patients with mitochondriopathy exhibit a wide range of neurologic symptoms and peripheral neuropathy can be considered to be an unusual clinical manifestation for a patient with a mitochondrial disease. In addition to a chronic axonal sensorimotor neuropathy, sensory ataxic neuropathy is more evocative and usually included in complex syndromes : NARP, SANDO, MNGIE. Mitochondriopathy is usually not considered as etiology for adult onset sensory ataxic neuropathy. Design/methods : We had the opportunity to observe 2 cases of sporadic adult-onset sensory ataxic neuropathy which can be attributed to multiple mitochondrial DNA deletions. Results : The first case concerns a 67 yrs man with ataxic symptoms onset at 47 yrs. ENMG revealed normal motor potentials and absent sensory potentials in the four limbs. Nerve biopsy showed a severe loss of myelinated fibres without any regenerative process. Muscle biopsy demonstrated a very few ragged red and Cox negative fibres. In skeletal muscle, we found multiple mt-DNA deletions by long-range PCR and southern blot analysis. No mutation were identified in the POLG1, TWINKLE and ANT1 genes. Ocular muscles involvement appeared only late in the clinical course at 65 yrs. The second case concerns a 50 yrs old woman who complained of ataxia since 20 yrs. A slow progression was reported, compatible with an unaided walking at 50 yrs. Ocular muscles were completely spared, even at 50 yrs and the peripheral neuropathy was isolated. Electrophysiological study showed no sensory potential in four limbs and reduced motor amplitude in lower limbs. In skeletal muscle, we found few mt-DNA deletions by long-range PCR and southern blot analysis. We analysed the coding region and exon/intron boundaries of the POLG1 gene by sequencing. The patient was heterozygous for both c.1391 T>C (M464T) and c.2302 A>G (K768E) misense mutations. Conclusion : Mitochondriopathy as a cause of isolated ataxic neuropathy has to be considered in adults, even after 40 yrs. This form is probably underdiagnosed and prevalence underestimated. Muscle mt-DNA analysis can be proposed as a main diagnostic marker.
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