Maekawa M, Kanno T, Sudo K
Department of Laboratory Medicine, Hamamatsu University School of Medicine.
Rinsho Byori. 1991 Feb;39(2):124-32.
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.
糖酵解是一个重要的能量产生系统。糖酵解途径中的酶异常会导致肌红蛋白尿，这些酶异常包括磷酸果糖激酶、磷酸甘油酸激酶、磷酸甘油酸变位酶和乳酸脱氢酶（LDH）缺乏。这些酶异常的常见症状是剧烈运动后出现肌肉痉挛、肌肉疼痛和横纹肌溶解。由肌红蛋白尿引起的急性肾衰竭是最值得注意的症状。在日常生活中，症状很少被观察到，预后通常良好。正确快速地诊断这种潜在的症状性疾病对于防止这些症状恶化很重要。LDH M亚基缺乏最初是通过尿液变色和实验室数据差异发现的。从那时起，日本人群中仅报告了4例。对缺血性前臂运动的反应具有特征性（缺血运动后未观察到静脉乳酸浓度升高，而发现静脉丙酮酸显著升高）。丙酮酸浓度升高在LDH-M亚基缺乏中具有特异性，在糖酵解途径的其他异常中未观察到。在患者肌肉中，糖酵解在甘油醛3-磷酸脱氢酶（GA3PD）步骤明显受阻，这可能是由于GA3PD活性产生的NADH再氧化受损所致。然后，过量的NADH通过α-甘油磷酸脱氢酶再氧化，磷酸丙糖被引流到α-甘油磷酸和甘油中。因此，ATP生成显著受损，肌肉组织受损。一项遗传学研究显示LDH-M亚基缺乏时外显子6中有20个碱基对缺失。这种突变导致移码翻译和提前终止。
