Complex I Deficiency

Complex I deficiency is the most common mitochondrial enzyme deficiency identified in children with mitochondrial cytopathy. Mutations can occur in either the mitochondrial DNA (e.g., ND1 and ND4) or nuclear DNA (e.g., NDUFV1 and NDUFS1). Leigh disease is characterized by psychomotor regression and often shows a predominantly gray matter involvement on MRI, although up to 28% of cases can initially present with a leukodystrophic pattern on MRI imaging. Lactate and alanine may be elevated in plasma, and urine may show an increase in 3-methylglutaconic acid or tricarboxylic acid intermediates; however, normal values do not rule out a complex I deficiency. Complex I deficiency is identified in skeletal muscle with many also showing a deficiency in fibroblasts. Seventy-five percent of children with complex I deficient Leigh disease die by 10. years of age. The presence of cardiomyopathy in a child with complex I deficiency is a significant negative predictor of outcome. Treatment of complex I deficiency is supportive (e.g., nutrition, spasticity management, and seizure control [when present]) and most children will receive some nutraceutical support to bypass the defect (coenzyme Q10, riboflavin), quench free radicals (alpha-lipoic acid, vitamin E), and provide alternative energy (creatine monohydrate).