1992 Volume 13 Issue 3 Pages 211-221
A Japanese boy with fatal pyruvate dehydrogenase deficiency died at 93h of age despite intensive treatment for a progressive metabolic acidosis and hyperammonemia. Enzymatic studies of the patient's liver and kidney homogenates revealed a decreased PDH complex activity caused by the absence of PDH component activity. This was further confirmed in that there were no immunoreactive proteins in positions corresponding to PDHα and β. All exon segments of genomic DNAs of PDHα and β isolated from the patient's liver and control leukocytes were amplified by PCR. Sequences of PCR-amplified products were compared with those of normal PDHα and β genes. Two single base-pair substitutions in two exons of the PDHα gene, one, G to T, in exon 5 and the other, T to C, in exon 6, were detected. These mutations generate a Phe-116 in the mature PDHα in place of the normal Cys-116 and a Pro-162 in place of the normal Leu-162. PCR-amplified exon segments of PDHα genomic DNA from the patient hybridized only to the mutant allele-specific oligonucleotide probes.
