Mitochondrial DNA point mutation T9176C in Leigh syndrome.

Leigh syndrome is a progressive neurodegenerative disease frequently associated with mitochondrial abnormalities. The mitochondrial DNA T9176C mutation in the adenosine triphosphatase 6 gene has recently been described as a cause of Leigh syndrome. Leukocyte DNA from 59 children with Leigh syndrome was screened for the T9176C mutation by conventional polymerase chain reaction methods. Two unrelated patients were found to be homoplasmic for this mutation in blood. Both patients had similar clinical and biochemical features. They had first presented acutely at 3 and 5 years, respectively, with ataxia and slurred speech. Magnetic resonance imaging changes were consistent with Leigh syndrome, and the cerebrospinal fluid lactate was elevated. They have both had relatively stable disease since the time of diagnosis. The mother of one of the children had presented at age 29 years with sudden onset of ataxia, headache, and blurred vision. She was heteroplasmic for the T9176C mutation. The T1976C is an important cause of Leigh syndrome especially in the subgroup of patients with more stable disease and normal respiratory chain enzyme analysis.