[Myoglobinuria due to enzyme abnormalities in glycolytic pathway--especially lactate dehydrogenase M subunit deficiency].
Glycolysis is an important energy productive system. Enzyme abnormalities the in glycolytic pathway, which cause myoglobinuria, are deficiencies of phosphofructokinase, phosphoglycerate kinase, phosphoglycerate mutase, and lactate dehydrogenase (LDH). Common symptoms of these enzyme abnormalities are muscle cramp, muscle pain, and rhabdomyolysis after strenuous exercise. Acute renal failure owing to myoglobinuria is the most noteworthy symptom. In daily life, symptoms are rarely observed and prognosis is usually good. Correct and fast diagnosis of such latent symptomatic disorders is important to prevent a turn for the worse of these symptoms. LDH M subunit deficiency was first discovered by urinary discoloration and a discrepancy of laboratory data. Since then, only four cases have been reported in the Japanese population. The response to ischemic forearm work is characteristic (an increase of venous lactate concentration after ischemic work is not observed and a marked increase of venous pyruvate is found). The increase of pyruvate concentration is specific in LDH-M subunit deficiency, and is not observed in other abnormalities of the glycolytic pathway. Glycolysis was markedly retarded in the patient's muscle in the glyceraldehyde 3-phosphate dehydrogenase (GA3PD) step, possibly due to the impaired reoxidation of NADH produced by GA3PD activity. Then, the excess NADH is reoxidized by alpha-glycerophosphate dehydrogenase and triose phosphates are drained to alpha-glycerophosphate and glycerol. Therefore ATP production is significantly impaired and muscle tissue is damaged. A genetical study revealed a deletion of 20 base-pairs in exon 6 in LDH-M subunit deficiency. This mutation results in a frame-shift translation and premature termination.
Maekawa
M
M
Department of Laboratory Medicine, Hamamatsu University School of Medicine.
Kanno
T
T
Sudo
K
K
D000293:Adolescent; D000328:Adult; D001483:Base Sequence; D001731:Bisphosphoglycerate Mutase / Q000172:deficiency; D005260:Female; D006019:Glycolysis; D006801:Humans; D007527:Isoenzymes; D007770:L-Lactate Dehydrogenase / Q000172:deficiency* / Q000235:genetics; D046911:Macromolecular Substances; D008297:Male; D008969:Molecular Sequence Data; D009212:Myoglobinuria / Q000209:etiology*; D010732:Phosphofructokinase-1 / Q000172:deficiency; D010735:Phosphoglycerate Kinase / Q000172:deficiency
D007527:Isoenzymes; D046911:Macromolecular Substances; D007770:L-Lactate Dehydrogenase; D010732:Phosphofructokinase-1; D010735:Phosphoglycerate Kinase; D001731:Bisphosphoglycerate Mutase