Thiamine Responsive Pyruvate Dehydrogenase Deficiency

Abstract

We studied a PDH deficient patient who is clinically responsive to thiamine. High Km and low Vmax values for the TPP were identified in the patient's cultured cells. Immunoblot analysis detected trace amount of mutant Ela polypeptide which was 3.5 KD larger than normal in size. Fournucleotide deletion in the Ela gene causes a reading frame shift, producing an abnormal polypeptide with additional 31 amino acids at C-teminus of the E1α subunit. The tryptophan (codon 383) and lysine (385) residues near the C-terminus might play a crucial role in the binding of TPP to the E1.