A novel GBE1 gene variant in a child with glycogen storage disease type IV.
Glycogen storage disease type IV is an autosomal recessive disorder of carbohydrates caused by deficiency of amylo-1-4-glycanoglycosyltransferase, which leads to accumulation of amylopectin-like polysaccharides in tissues including liver, heart and neuromuscular system. More than 40 different mutations in the glycogen branching enzyme gene (GBE1) have been described. In this study, we report a 2-year-old boy who presented with developmental delay and muscle weakness. He subsequently was diagnosed with glycogen storage disease type IV based on a liver biopsy histology and electron microscopy. Glycogen branching enzyme activity was in the low range. Genetic analysis demonstrated a novel heterozygous variant (c.760A>G; p.Thr254Ala) in exon 6 of the GBE1 gene, which is believed to be pathogenic. This variant was inherited from the patient's mother who was asymptomatic with normal glycogen branching enzyme activity. Whole-exome sequencing failed to reveal additional variations in the GBE1 gene.
Division of Anatomic Pathology, Mayo Clinic, Rochester, MN, United states, 55905. Electronic address: said.samar@mayo.edu.
Samar M
SM
Said
Division of Medical Genetic, Mayo Clinic, Rochester, MN, United states, 55905.
Marine I
MI
Murphree
Division of Anatomic Pathology, Mayo Clinic, Rochester, MN, United states, 55905.
Taofic
T
Mounajjed
Division of Gastroenterology, Mayo Clinic, Rochester, MN, United states, 55905.
Mounif
M
El-Youssef
Division of Anatomic Pathology, Mayo Clinic, Rochester, MN, United states, 55905.
Lizhi
L
Zhang
D001706:Biopsy; D002675:Child, Preschool; D005091:Exons; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D006004:Glycogen Debranching Enzyme System / Q000172:deficiency / Q000235:genetics*; D006011:Glycogen Storage Disease Type IV / Q000175:diagnosis / Q000201:enzymology / Q000235:genetics*; D040941:Heredity; D006579:Heterozygote; D006801:Humans; D008099:Liver / Q000201:enzymology / Q000648:ultrastructure; D008297:Male; D008854:Microscopy, Electron; D025202:Molecular Diagnostic Techniques; D010375:Pedigree; D010641:Phenotype
D006004:Glycogen Debranching Enzyme System; C577876:GBE1 protein, human
Glycogen branching enzyme; Glycogen storage disease; Hepatocyte inclusions; Liver biopsy; Novel GBE1 variant