Hepatic and neuromuscular forms of glycogen storage disease type IV caused by mutations in the same glycogen-branching enzyme gene

摘要: Glycogen storage disease type IV (GSD-IV) is an autosomal recessive resulting from deficient glycogen-branching enzyme (GBE) activity. The classic and most common form progressive liver cirrhosis failure leading to either transplantation or death by 5 yr of age. However, the not always progressive. In addition, a neuromuscular has been reported. molecular basis GSD-IV known, nor there known reason for clinical variability. We studied GBE gene in patients with various presentations GSD-IV. Three point mutations were found two classical presentation: R515C, F257L, R524X. Transient expression experiments showed that these inactivated Two mutations, L224P Y329S, detected separate alleles patient nonprogressive hepatic form. resulted complete loss activity, whereas Y329S approximately 50% allele was also another but 35 unrelated controls more severe forms A 210-bp deletion nucleotide 873 1082 cDNA fatal neonatal presentation. This deletion, representing one full exon, caused 3' acceptor splicing site mutation (ag aa). abolished Our studies indicate three different same gene. data suggest significant retention activity may be mild disease. Further study genotype/phenotype correlations yield useful information predicting outcomes.