| Research Abstract |
Glycogen storage disease type III is a disorder caused by a genetic deficiency in glycogen debranching enzyme (gene symbol : AGL), characterized by an excessive accumulation of abnormal glycogen in the liver or muscles. We have identified 12 AGL mutations, 5 nonsense (R34X, W225X, R864X, Y1148X and W1327X), 4 splicing mutations (IVS7+SG>A, IVS 14+1G>T, IVS21+1G>A and IVS32-12A>G), 2 small deletions (750-753delAGAC and 1019delA) and a point mutation in the promoter region (-949C>T)]. Among them, 7 mutations, R34X, W225X, Y1 148X, IVS7+5G>A, 750-753delAGAC, 1019delA, and -949C>T, are novel. All but the promoter mutation are predicted to result in truncated proteins lacking the C terminal and are nonfunctioning, suggesting that a glycogen-binding domain located at the region is important for proper AGL function. Some AGL mutations are found in several different ethnic groups. This is the first AGL mutation report for Turkish, Egyptian, German and Canadian populations. Patients with IVS32-12A>G had milder muscular manifestations. ^<31>P-NMR spectroscopy showed alkalinization in intracellular pH during exercise, compared with controls.
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