Mitochondrial Complex I Deficiency, Nuclear Type 4

A number sign (#) is used with this entry because of evidence that mitochondrial complex I deficiency nuclear type 4 (MC1DN4) is caused by homozygous or compound heterozygous mutation in the NDUFV1 gene (161015) on chromosome 11q13.

For a discussion of genetic heterogeneity of mitochondrial complex I deficiency, see 252010.

Clinical Features

Schuelke et al. (1999) reported 2 brothers with complex I deficiency with mutations in the NDUFV1 gene. Pregnancy, delivery, and early infancy were normal in both children. At the age of 5 months, they presented with repeated vomiting and developed strabismus, progressive muscular hypotonia, myoclonic epilepsy, and psychomotor regression. Cranial CT scans showed brain atrophy, but cranial MRIs were not available to confirm Leigh syndrome. Lactate and pyruvate concentrations in blood and cerebrospinal fluid were elevated. Isolated complex I deficiency was demonstrated in muscle and cultured fibroblasts. The boys died at 14 and 17 months from aspiration pneumonia. In another child with complex I deficiency Schuelke et al. (1999) reported another child with complex I and mutation in the NDUFV1 gene. Features included infantile myoclonic epilepsy, spasticity, psychomotor regression, and macrocephaly. Serial cranial MRI scans showed brain atrophy and a progressive macrocytic leukodystrophy. At age 10 years, she had severe spasticity and blindness.

Benit et al. (2001) reported an infant with complex I deficiency caused by mutations in the NDUFV1 gene. He was first hospitalized at age 1 year for seizures and moderately elevated levels of plasma lactate. Other features included cerebellar ataxia, psychomotor regression, strabismus, and ptosis. Magnetic resonance imaging showed brain atrophy in multiple symmetric areas of hyperintensity in the brainstem. He died at age 3 years of an acute episode of metabolic acidosis.

Molecular Genetics

In 3 of 20 patients with isolated complex I deficiency, Schuelke et al. (1999) detected homozygous or compound heterozygous mutations in the NDUFV1 gene (161015.0001-161015.0003).

In a series of 36 patients with mitochondrial complex I deficiency, Benit et al. (2001) identified 3 patients carrying a total of 6 mutations in the NDUFV1 gene (see, e.g., 161015.0004 and 161015.0005).