Leigh-type neuropathology in Pearson syndrome associated with impaired ATP production and a novel mtDNA deletion.

Pearson syndrome is a systemic disorder of oxidative phosphorylation in infants, predominantly affecting the bone marrow and exocrine pancreas and associated with single deletions in mitochondrial DNA (mtDNA). CNS involvement may occur in patients who survive the infantile hematopoietic disorder. We describe a Pearson syndrome patient who developed neurologic manifestations associated with the pathologic features of Leigh syndrome. Biochemical studies in muscle and skin fibroblasts showed partial deficiencies of complexes I and IV of the respiratory chain. Adenosine triphosphate production in mitochondria isolated from skin fibroblasts was reduced to 25% of controls. We detected a novel 3.6 Kb mtDNA deletion in skin fibroblasts from the proband but not in his mother's white blood cells. Leigh syndrome seems to be the common neuropathologic expression of any disorder causing severe impairment of oxidative energy production in the CNS.