We report the case of a 62-year-old man with
sensory ataxic neuropathy, dysarthria, and ophthalmoparesis (
SANDO). He developed gait disturbance at 54 years of age,
muscle weakness at 56 years, and difficulty hearing at 58 years. His brother had
muscle weakness in both legs from age 20 years, and was diagnosed with
Charcot-Marie-Tooth disease because he had
muscle weakness of the four extremities, decreased CMAP and SNAP amplitudes on peripheral nerve conduction tests, and loss of large myelinated fibers and onion-bulb formations on sural nerve biopsy. His brother died aged 46 years, but no accurate cause of death was identified. Neurological examination of the present patient revealed bilateral ptosis, external
ophthalmoparesis,
dysarthria,
dysphagia,
sensorineural hearing loss, mild weakness and
atrophy of proximal muscles in all four limbs, severe
sensory ataxia, and disturbance of deep sensation in his legs. He showed elevation of
lactate and
pyruvate levels in cerebrospinal fluid and serum. An aerobic exercise test disclosed a marked increase in
lactate and
pyruvate levels in serum. On nerve conduction study, amplitudes of CMAP and SNAP, and F wave-evoked frequency were decreased. Needle electromyography showed chronic neurogenic patterns with fibrillation potentials in the extremity muscles. Head MRI demonstrated T2 prolonged lesions in the bilateral basal ganglia, while brain MRS revealed a small
lactate peak. Biopsy of his left lateral vastus muscle showed ragged-red fibers and group
atrophy, and some muscle fibers had decreased
cytochrome c activity. Left sural nerve biopsy revealed a marked loss of large myelinated fibers, and some onion-bulb formations. Genetic testing disclosed a large
mtDNA deletion in the biopsied muscle. Among nuclear genes, we found point mutations in ANT-1 (exon 1 c.105G>A,
5' untranslated region) and POLG-1 (exon 4, c.1218G>A, p. and exon 23 c.3920C>T, p.A1217V). We diagnosed
SANDO. This is the first case of
SANDO with large
mitochondrial DNA deletions in Japanese.