Pyruvate Dehydrogenase E3-Binding Protein Deficiency

Pyruvate dehydrogenase E3-binding protein deficiency is a rare mild form of pyruvate dehydrogenase deficiency (PDHD, see this term) characterized by variable lactic acidosis and neurological dysfunction.

Epidemiology

Prevalence is unknown. About 20 cases have been reported to date. The disorder is more frequent than PDHD E2 deficiency but less frequent than E1-alpha deficiency (see these terms).

Clinical description

Patients usually present with neonatal lactic acidosis or with delayed development and hypotonia during infancy. In contrast to other forms of pyruvate dehydrogenase deficiency, patients with E3 binding protein deficiency often survive well into childhood or adult life as there is some assembly of the pyruvate dehydrogenase complex even with complete deficiency of this protein. Thinning or agenesis of the corpus callosum is a common finding on MRI imaging of the brain.

Etiology

PDHD E3 binding protein deficiency is caused by a mutation in the PDHX gene (11p13) encoding the E3 binding protein subunit; also known as component X of the pyruvate dehydrogenase complex.

Genetic counseling

The pattern of inheritance is autosomal recessive.