Abnormal subunit profile of oxphos complexes by electrophoresis and tandem-MS in a neonate with severe congenital lactic acidosis.

Proposita presented with low birth weight, hypotonia, respiratory insufficiency and hepatomegaly. Laboratory investigations revealed a combined metabolic and respiratory acidosis, anemia and high blood lactate (21mM). The patient was ventilated and received massive bicarbonate infusions for correction of metabolic acidosis. Her condition stabilized but acidosis and increased blood lactate concentrations (17mM on D2) persisted. Bilateral adrenal calcifications were detected. The patient remained ventilator dependent and developed hepatosplenomegaly and extreme cardiomegaly. Brain ultrasound showed lesions in basal ganglia on the left. Her condition deteriorated and she died at the age of one month as a result of cardiopulmonary insufficiency. OXPHOS complex activities were normal in fibroblasts, skeletal muscle and heart muscle. In liver, a severe combined deficiency of catalytic activity of complexes I, III, IV and V were found spectrophotometrically and confirmed by catalytic staining in the blue native gel. MtDNA analysis did not reveal any abnormality. Two dimensional gel electrophoresis showed a decrease of several subunits of complex I, III and IV. The subunit composition of complex V was abnormal as shown by immunoblotting using antibodies against complex V subunits. Tandem mass spectrometry was used for protein identification.