The course and metabolic profile of a novel mitochondrial disease with ATPase deficiency and mutation in the TMEM70 gene are described in a retrospective multisite survey of 25 patients (14 boys, 11 girls) from 7 European countries. The infants were born with severe muscular hypotonia (92%), apneic spells (92%), cardiomyopathy (76%), lactic acidosis (92%), hyperammonemia (86%), and 3-methylglutaconic aciduria (100%). Ten died within the first 6 weeks after birth. Surviving infants had persistent muscular hypotonia and psychomotor delay, with microcephaly in 13/22. Boys had hypospadia in 54% and cryptorchidism in 67%. [1]

COMMENT. ATP synthase deficiency due to TMEM70 mutation is a novel mitochondrial disease of neonatal onset with muscle hypotonia, hypertrophic cardiomyopathy, lactic acidosis, hypospadius, hyperammonemia, and 3-methylglutaconic aciduria. Progressive CNS impairment affects most patients who survive the neonatal period, but the severity of the phenotype may vary. Molecular genetic diagnosis is available without need for muscle biopsy. TMEM70 deficiency should be considered in critically ill hypotonic neonates.