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Clinical characteristics and gene mutation analysis of one pedigree with glycogen storage disease type IV

Sinian Pan, Shunye Zhu, Muxue Yu

Glycogen Storage Disease type IV (GSD-IV; also known as Andersen disease) is a rare autosomal recessive disorder of glycogen metabolism caused by mutations in the Glycogen-Branching Enzyme 1 (GBE1) gene that encodes the 1,4-α-glucan-branching enzyme. The aim of this study is to identify the mutation of GBE1 gene in a family with GSD IV. A 17-month-old Chinese girl with hepatosplenomegaly was admitted to the Third Affiliated Hospital of Sun Yat-sen University (Guangzhou, China). She had shown signs of jaundice and failure to thrive. The peripheral blood samples from the proband and her parents and two older brothers were collected, and the pathogenic genes and mutational sites of the proband were screened by the next generation sequencing and verified by Sanger sequencing. In the family, the proband carried a homozygous GBE1 gene NM_000158: c.1571G>A: (p.Arg524Gln) mutation, while her parents and the younger brother carried a heterozygous mutation of c.1571G>A: (p.Arg524Gln). The mutation has been proved to be a rare mutation with frequency no greater than 0.01 in ExAC_ALL, ExAC_SAS and ExAC_EAS databases. The older brother was normal. The diagnosis of GSD IV was established and liver transplantation was recommended to her. The parents declined the liver transplantation. She died of liver failure at 22 months of age. This is the first homozygous mutation of GBE1 gene causing GSD IV being reported in mainland China. The identified mutations add to the list of GBE1 mutations of the hepatic form of GSD-IV.