Lactate dehydrogenase M-subunit deficiency: a new type of hereditary exertional myopathy

Clin Chim Acta. 1988 Mar 31;173(1):89-98. doi: 10.1016/0009-8981(88)90359-2.


Three families with a complete deficiency of the lactate dehydrogenase M subunit show exertional myoglobinuria. The response to ischemic forearm work is characteristic in these three families: an increase of venous lactate concentration after ischemic work was not observed and a marked increase of venous pyruvate was found. Glycolysis was markedly retarded in the patient's muscle in the glyceraldehyde 3-phosphate dehydrogenase (GA3PD) step. A significant increases in glyceraldehyde 3-phosphate, dihydroxyacetone phosphate and fructose 1,6-diphosphate were observed. The glycolysis retardation may be attributed to the impaired reoxidation of NADH produced by GA3PD action. The cytosolic fraction of skeletal muscle is rich in alpha-glycerophosphate dehydrogenase. This enzyme reoxidizes the excess NADH and drains triose phosphates from the glycolytic pathway under anaerobic conditions. For this reason, ATP production was significantly impaired and muscle cells were damaged in these patients. Consequently, the cytosolic enzymes and proteins such as creatine kinase and myoglobin were released into the blood stream. Otherwise, patients with a lactate dehydrogenase M-subunit deficiency do not show muscle stiffness and myoglobinuria under ordinary circumstances. They complain of muscle rigidity and sudden myoglobinuria after strenous exercise under anaerobic conditions. Thus, the lactate dehydrogenase M-subunit deficiency does not show any symptoms under ordinary circumstances, but is a latent hereditary disorder, now recognized as a new type of hereditary exertional myoglobinuria.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Female
  • Humans
  • Isoenzymes
  • L-Lactate Dehydrogenase / deficiency*
  • Male
  • Myoglobinuria / enzymology*
  • Myoglobinuria / genetics
  • Myoglobinuria / immunology
  • Physical Exertion
  • Rhabdomyolysis / enzymology*


  • Isoenzymes
  • L-Lactate Dehydrogenase