Congenital hydranencephalic-hydrocephalic syndrome associated with mitochondrial dysfunction

We report the case of a 3-year-old girl, the only child of a nonconsanguine ous couple without relevant antecedents, who was born with hydranencephalic -hydrocephalic syndrome diagnosed by ultrasonography at gestation week 28, and who was treated during the neonatal period by implantation of a ventric uloperitoneal shunt. She showed severe mental retardation, and died at age 4 years following an acute respiratory infection. Due to persistently high lactic acid levels in blood, muscle and skin biopsies were taken. Analysis of muscle biopsies revealed microscopic and ultrastructural alterations typ ical of mitochondrial disorders, and low levels of complexes III and IV of the mitochondrial respiratory chain. The enzymes of the pyruvate dehydrogen ase complex showed normal activities in cultured skin fibroblasts. These fi ndings raise the possibility that at least some cases of congenital hydrane ncephalic-hydrocephalic syndrome may be due to alterations in the mitochond rial respiratory chain.