Alpers-Huttenlocher syndrome: mitochondrial diseases of brain and liver

Objective: Alpers-Huttenlocher syndrome comprises progressive neurodegenerative disorders with liver disease, the etiology of which is not yet known. To gain insight into the pathogenesis, we investigated the case of a patient who had this disorder.

Case report: The patient developed normally in the first 6 months. Refusal of food and failure to thrive were noted from the 7th month of life. At the age of 1 year, he had an infection during which increased transaminase levels were detected. Hepatomegaly with abnormally dense liver tissue was diagnosed sonographically. Motor development was delayed. His condition gradually deteriorated. Further, hypoglycemia and lactate acidosis occurred. A liver biopsy at the age of 16 months revealed necroses and steatosis. He developed epilepsy with episodes of status epilepticus at 20 months of age. An increase in lactate and a decrease in choline and inositol were detected by MRS of the brain. Reduced complex II activity of the respiratory chain was observed in fibroblasts. The patient died at 2 years following status epilepticus. Autopsy showed liver fibrosis with transition to liver cirrhosis, spongiform changes in the cerebrum, focal infarcts in the cerebellar cortex, and Ammon’s horn sclerosis. Abnormal mitochondria (Chow & Thorburn, 2000) were found in liver, heart muscle, and brain.

Conclusion: In the case of an infant with rapidly progressive Alpers-Huttenlocher syndrome, lactate acidosis, MRS findings, a respiratory chain defect, and abnormal mitochondria supported the hypothesis that mitochondrial defects underlie these disorders.

Key Words: neurodegenerative disorders, hepatopathy, lactate acidosis