Kanno T, Maekawa M
Department of Laboratory Medicine, Hamamatsu University School of Medicine, Japan.
Muscle Nerve Suppl. 1995;3:S54-60. doi: 10.1002/mus.880181413.
Lactate dehydrogenase M-subunit deficiency was first reported 1980 as an exertional myoglobinuria. Since then, 6 Japanese and 3 Caucasian families have been reported. Also, typical skin lesions were observed in 1 Japanese patient. Since then, 2 families, one Japanese and one Caucasian, have been found with this typical skin eruption. The metabolic background of exertional myoglobinuria was demonstrated as a result of the impaired reoxidation of NADH produced by glyceraldehyde-3-phosphate-dehydrogenase (G3PD) action. The excess NADH was partly reoxidized by the action of alpha-glycerophosphate dehydrogenase abundant in cytosolic fraction of skeletal muscle. This enzyme reoxidizes excess NADH simultaneously draining out triose phosphate from the glycolytic pathway. Abortive glycolysis results in impaired ATP production followed by rhabdomyolysis. Genomic analysis revealed the heterogeneities of the mutations of this disease.
乳酸脱氢酶M亚基缺乏症于1980年首次被报道为运动性肌红蛋白尿。从那时起，已有6个日本家庭和3个高加索家庭被报道。此外，在1例日本患者中观察到典型的皮肤病变。从那时起，又发现了2个家庭，一个是日本家庭，另一个是高加索家庭，都有这种典型的皮肤疹。运动性肌红蛋白尿的代谢背景被证明是由于甘油醛-3-磷酸脱氢酶（G3PD）作用产生的NADH再氧化受损所致。过量的NADH部分通过骨骼肌胞质部分中丰富的α-甘油磷酸脱氢酶的作用而被再氧化。这种酶在从糖酵解途径排出磷酸丙糖的同时使过量的NADH再氧化。不完全糖酵解导致ATP生成受损，继而发生横纹肌溶解。基因组分析揭示了该疾病突变的异质性。
