Mutation of NDUFAF2 Linked to Mitochondrial Complex I Deficiency

Mitochondrial complex I deficiency is an autosomal recessive disorder caused by homozygous mutations in the reduced form of nicotinamide adenine dinucleotide (NADH). It is characterized by a wide range of signs and symptoms that affect numerous human systems and organs. This disease causes neurological issues, including encephalopathy, recurrent epilepsy, intellectual disability, ataxia, and involuntary movements. The initial step of the mitochondrial respiratory chain, during which protons are transported across the inner mitochondrial membrane along with electron transfer from NADH to ubiquinone, is catalyzed by NADH: ubiquinone oxidoreductase. In this case report, we describe a patient presenting with severe, rapidly progressive neurological loss who harbored a novel mutation in <i>NDUFAF2</i> identified using exome sequencing. At six months of age, her mother noticed delayed motor development. Thereafter, the patient developed metabolic acidosis and abnormal movements, mimicking seizures triggered by aspiration pneumonia, with elevated serum lactate levels. Genetic testing revealed a c.127G>A mutation in <i>NDUFAF2</i>, consistent with mitochondrial complex I deficiency. This case highlights the utility of exome sequencing as a powerful and cost-effective tool for diagnosing clinically heterogeneous disorders such as mitochondrial diseases. Mitochondrial complex I deficiency is an important differential diagnosis in patients with recurrent central hypoventilation. Our findings expand the mutational spectrum of this rare disease.