Complex V (Adenosine triphosphate [ATP] synthase) couples proton flow from the intermembraneous space back to the mitochondrial matrix with the conversion of ADP and inorganic phosphate to ATP. Mitochondrial ATP synthase is a multi-subunit enzyme that catalyzes ATP synthesis during oxidative phosphorylation. The complete loss of ATP synthase enzyme activity is most likely incompatible with life. However, partial loss or Complex V deficiency, reflected by a lower amount of functional ATP-synthase, causes a medical condition characterized by progressive myopathy, hypertrophic cardiomyopathy, seizures, and severe lactic acidosis. It is often associated with evidence of brainstem degeneration leading to coma. The presence of methyl glutaconic aciduria can be a major clue in the diagnosis of Complex V deficiency in an infant. Only a few cases have been described in the literature. The clinical features include mental retardation, craniofacial dysmorphism with prominent nasal bridge, micro-/retrognathia and low-set ears, and genital anomalies (cryptorchidism, hypospadias). Progressive muscle hypotonia, hypertrophic cardiomyopathy, hepatomegaly, severe lactic acidosis, hyperammonemia, and intermittent 3-methylglutaconic aciduria are often present. Death usually occurs within the first week of life and is caused by heart failure.
ATPase Deficiency; ATP Synthase Deficiency.
Autosomal recessive with the genetic defect affecting ATP Synthase (ATPAF2, Mitochondrial F1 Complex, Assembly Factor 2) gene, which has been mapped to chromosome 17p11.2.