[Diagnostic clue and genomic analysis of LDH-M subunit deficiency]

Lactate dehydrogenase (LDH) M(A) subunit deficiency was first discovered by urinary discoloration and a discrepancy of laboratory data. Since then, five other families with this disorder have been reported in the Japanese population. The response of pyruvate concentration after forearm ischemic work is specific for LDH-M subunit deficiency. During strenuous exercise ATP production is significantly impaired and muscle tissue is damaged. A genetic study revealed a deletion of 20 base-pairs in exon 6 of the LDH-M gene in four families that were homozygous and one family that was heterozygous for LDH-M subunit deficiency. This mutation results in a frame-shift translation and premature termination. In addition to this mutation, we found a nonsense mutation at codon 328 in exon 7 in an individual heterozygous for LDH-M subunit deficiency, and a deletion of 3 base-pairs, TGT at codon 127 in exon 3 in a proposita who was homozygous and in her parents who were heterozygous for LDH-M subunit deficiency in the fifth family. Therefore, molecular heterogeneities were revealed in genetic mutations of LDH-M subunit deficiency.