Prenatal Diagnosis of Glycogen Storage Disorder Type III.

Among glycogen storage disorders, deficiency of glycogen debranching enzyme causes an incomplete glycogenolysis resulting in glycogen accumulation with abnormal structure in liver and muscle. This report describes a novel mutation in a family with glycogen storage disorder Type III in index child used in prenatal diagnosis in the fetus in second trimester.

AGL gene mutation and clinical features in Korean patients with glycogen storage disease type III

PURPOSE: Glycogen storage disease type III (GSD-III) is a rare autosomal recessive disorder of glycogen metabolism. The affected enzyme, amylo-1,6-glucosidase, 4-alpha-glucanotransferase (AGL, glycogen debranching enzyme), is responsible for the debranching of the glycogen molecule during catabolism. The disease shows clinical and biochemical heterogeneity, reflecting genotype-phenotype heterogeneity among different patients. In this study, we aim at analyzing mutations of the AGL gene in three unrelated Korean GSD-III patients, and characterizing their clinical and laboratory findings. METHODS: We characterized the clinical features of three unrelated Korean GSD-III patients by biochemical, histological and imaging studies. The 35 exons and part of exon-intron boundaries of AGL were analyzed by direct sequencing using genomic DNA extracted from the peripheral leukocytes of patients. RESULTS: Diverse clinical features were observed in these patients including hepatomegaly (all patients), seizures (patient 2), growth failure (patients 1 and 2), hyperlipidemia (patients 1 and 3), raised transaminase and creatine kinase concentrations (all patients), and mild cardiomyopathy (patient 2). Liver transplantation was performed in patient 2 due to progressive hepatic fibrosis. Administration of uncooked corn starch maintained normoglycemia and improved biochemical and growth profiles. DNA sequence analysis revealed mutations in 5 out of 6 alleles. Patient 1 was a compound heterozygote of c.1282 G>A (p.R428K) and c.1306delA (p.S603PfsX6), patient 2 had c.1510_1511insT (p.Y504LfsX10), and patient 3 had c.3416 T>C (p.L1139P) and c.1735+1 G>T (p.Y538_R578delfsX4) mutations. Apart from the p.R428K mutation, the 4 other substitutions identified were novel. CONCLUSION: GSD-III patients display variable phenotypic characteristics resembling those of GSD-Ia. Molecular defects in the AGL gene of Korean GSD-III patients are genetically heterogeneous.