[Dichloroacetate treatment for adult patients with mitochondrial disease]

We report beneficial and adverse effects of sodium dichloroacetate (DCA) in three adult Japanese patients with mitochondrial disease: a 21-year-old male with involuntary movements, optic atrophy, hearing loss, and convulsions (patient 1), a 28-year-old man with mental deterioration, hemianopia, hearing disturbance, and convulsions (patient 2), and a 50-year-old woman with hearing disturbance, generalized muscle atrophy, and insulin dependent diabetes mellitus (patient 3). A3243G mutation was found in patient 2 and patient 3. Oral administration of DCA improved consciousness level and gait disturbances in patient 1, and ameliorated headaches, easy fatiguability, and muscle cramps in patient 2 and patient 3. DCA normalized high levels of lactate and pyruvate in blood and cerebrospinal fluids in all three patients. In patient 3, daily insulin needs decreased from 38 to 24 units, and urine C peptide increased from an undetectable level to 16 micrograms/day. In patient 1, DCA 23 mg/kg/day had been beneficial without adverse effects and he became free of convulsions for more than 32 months. However, despite of normal lactate and pyruvate, unsteady gait and lethargy developed after 50 mg/kg/day treatment for two months and one month in patient 2 and patient 3, respectively. In both patients, deep tendon reflexes disappeared and Romberg sign became positive. Nerve conduction studies confirmed sensory-dominant polyneuropathy and electroencephalogram showed diffuse slow basic activities. Cessation of DCA resulted in recovery of gait and consciousness, but sensory nerve action potentials did not recover in one month. Long term treatment of 50 mg/kg/day DCA may affect adversely the peripheral and central nervous systems in adult patients. Although effective plasma DCA concentration was previously reported as 25-160 micrograms/ml in patients under 18 years old, plasma DCA concentration of 10.2 micrograms/ml was sufficient in patient 1. We recommend lower dose of DCA in adult patients than in child patients.