Mitochondrial Complex I Deficiency / Leigh Syndrome (NDUFS4)
Pathogenic variants in the gene NDUFS4 cause autosomal recessive mitochondrial disorders as a result of defective oxidative phosphorylation, a system that is involved in cellular energy production. These disorders often manifest with neuromuscular symptoms. This gene encodes an accessory subunit of complex I of the mitochondrial respiratory chain.
- Mitochondrial complex I deficiency has a clinically progressive course with no increased lactate concentrations in body fluids. Hypotonia at birth is followed by severe vomiting, failure to thrive, psychomotor retardation, and seizures.
- Leigh syndrome is an early-onset progressive neurodegenerative disorder with a rapid course and characteristic neuropathology including focal, bilateral lesions in specific regions in the central nervous system. The onset of this condition occurs early in life and is characterized by ataxia, loss of muscle strength, and neurodegeneration. Other clinical manifestations include psychomotor delay, hypotonia, seizures, lactic acidosis, and basal ganglia lesions at birth.
There are no clear genotype-phenotype correlations. Life expectancy is often shortened and death may occur in childhood.
For information about carrier frequency and residual risk, please see the residual risk table.