Complex I deficiency caused by recessive mutations in the NUBPL gene is an early onset (typically in 3-18 months olds) mitochondrial disorder most commonly presenting with cerebellar dysfunction, which manifests as developmental delay (e.g., ataxia and dysarthria). Complex I, a holoenzyme comprising 44 proteins (encoded by nuclear and mitochondrial genes), is the largest enzyme of the electron transport chain. At least 38 complex I genes have been reported to cause recessive mitochondrial disease. Presently, worldwide only 15 families with an affected child have been reported to have NUBPL complex I deficiency.
NUBPL