Pyruvate Dehydrogenase E1-Beta Deficiency

A number sign (#) is used with this entry because pyruvate dehydrogenase E1-beta deficiency is caused by homozygous mutation in the PDHB gene (179060) on chromosome 3p14.

For a general phenotypic description and a discussion of genetic heterogeneity of pyruvate dehydrogenase deficiency, see 312170.

Clinical Features

Brown et al. (2004) reported 2 unrelated patients with pyruvate dehydrogenase deficiency. The first patient, the son of first-cousin parents, was investigated at age 3 months because of lactic acidosis and hypotonia. Two previous sibs had died early, one with lactic acidosis. The patient developed metabolic acidosis on day 1. He required ventilation from day 3 to day 22. MRI demonstrated agenesis of the corpus callosum. At age 3 months, he showed global hypotonia and reduced reflexes. He developed severe lactic acidosis following general anesthesia for muscle biopsy and lumbar puncture. He suffered respiratory arrest but was successfully treated with ventilation and bicarbonate. The second patient, also the son of consanguineous parents, was hypotonic at birth with poor respiratory effort. He was investigated at 9 weeks of age because of continuing hypotonia, lack of visual attention, and respiratory stridor. MRI of the brain was normal. He made little developmental progress and died at 12 months of age.

Molecular Genetics

In 2 unrelated patients with pyruvate dehydrogenase deficiency, Brown et al. (2004) identified homozygous mutations in the PDHB gene (179060.0001-179060.0002).