Cloning of Dimethylglycine Dehydrogenase and a New Human Inborn Error of Metabolism, Dimethylglycine Dehydrogenase Deficiency

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• 作者：Barbara A. Binzak ; Ron A. Wevers ; Sytske H. Moolenaar ; Yu-May Lee ; Wuh-Liang Hwu ; Jo Poggi-Bach ; Udo F.H. Engelke ; Heidi M. Hoard ; Joseph G. Vockley ; Jerry Vockley
• 刊名：The American Journal of Human Genetics
• 出版年：2001
• 出版时间：April 2001
• 年：2001
• 卷：68
• 期：4
• 页码：839-847
• 全文大小：2141 K

文摘

Dimethylglycine dehydrogenase (DMGDH) (E.C. number 1.5.99.2) is a mitochondrial matrix enzyme involved in the metabolism of choline, converting dimethylglycine to sarcosine. Sarcosine is then transformed to glycine by sarcosine dehydrogenase (E.C. number 1.5.99.1). Both enzymes use flavin adenine dinucleotide and folate in their reaction mechanisms. We have identified a 38-year-old man who has a lifelong condition of fishlike body odor and chronic muscle fatigue, accompanied by elevated levels of the muscle form of creatine kinase in serum. Biochemical analysis of the patient’s serum and urine, using ¹H-nuclear magnetic resonance NMR spectroscopy, revealed that his levels of dimethylglycine were much higher than control values. The cDNA and the genomic DNA for human DMGDH (hDMGDH) were then cloned, and a homozygous A→G substitution (326 A→G) was identified in both the cDNA and genomic DNA of the patient. This mutation changes a His to an Arg (H109R). Expression analysis of the mutant cDNA indicates that this mutation inactivates the enzyme. We therefore confirm that the patient described here represents the first reported case of a new inborn error of metabolism, DMGDH deficiency.