Pyruvate dehydrogenase deficiency due to a 20-bp deletion in exon II of the pyruvate dehydrogenase (PDH) E1 alpha gene.

A 20-bp deletion in the last exon of the pyruvate dehydrogenase (PDH) E1 alpha gene was found in a severely affected female patient diagnosed with PDH deficiency. PDH-complex activity in the patient's fibroblasts was 22% of that in normal controls. The mutation was characterized using PCR techniques with both patient cDNA and genomic DNA, followed by sequencing of the products. E1 beta cDNA sequence was found to be the same as that in controls. The deletion causes a frameshift and the occurrence of a premature stop codon. Western blot analysis revealed an extra band migrating just above the PDH E1 beta band. Northern blot analysis showed normal levels of both E1 alpha and E1 beta message when probed with the respective cDNAs. However, a larger intermediate-size transcript was observed for this patient in the E1 beta blot. The 20-bp deletion was not found in either parent's genomic DNA, and hence we conclude that the mutation must have occurred de novo, either in the germ-line cells or immediately following fertilization.