title: The variable clinical phenotype of three patients with hepatic glycogen synthase deficiency.
abstract: BACKGROUND
  Glycogen synthase deficiency, also known as glycogenosis (GSD) type 0 is an inborn error of glycogen metabolism caused by mutations in the GYS2 gene, which is transmitted in an autosomal recessive trait. It is a rare form of hepatic glycogen storage disease with less than 30 cases reported in the literature so far. The disorder is characterized by fasting hyperketotic hypoglycemia without hyperalaninemia or hyperlactacidemia. It is a glycogenosis with lack of liver glycogen synthesis, therefore hepatomegaly is not observed in patients with glycogen synthase deficiency. Symptoms of fasting hypoglycemia in patients with glycogen storage disease type 0 (GSD0) usually appear for the first time in late infancy when weaning from overnight feeds. Seizures associated with low blood glucose may also occur, but they are rare. Clinical management is therefore based on frequent meals composed of high protein intake during the day and addition of uncooked cornstarch in the evening.
  
  
  METHODS
  Herein we report three new cases of liver glycogen synthase deficiency (GSD0). The first patient presented at the 4 years of age with recurrent hypoglycemic seizures. The second patient who is the brother of the first patient presented at 15 months with asymptomatic incidental hypoglycemia. Glucose monitoring in both patients revealed daily fluctuations from fasting hypoglycemia to postprandial hyperglycemia and lactic acidemia. A third patient was consulted for ketotic hypoglycemia and postprandial hyperglycemia at the 5 years of age.
  
  
  CONCLUSIONS
  Genetic analyses of the siblings revealed homozygosity for mutation c.736C>T on the GYS2 gene confirming the diagnosis. The third patient was found to be homozygous for c.1145G>A. GSD0 is more common than previously assumed. Recognition of the variable phenotypic spectrum of GSD0 and routine analysis of GYS2 are essential for the correct diagnosis.
authors.affiliation: Department of Pediatric Metabolism and Nutrition, Dr Sami Ulus Child Hospital, Ankara.
authors.forename: Çiğdem Seher
authors.initials: ÇS
authors.lastname: Kasapkara
authors.affiliation: Division of Pediatric Endocrinology, Dr Sami Ulus Child Hospital, Ankara.
authors.forename: Zehra
authors.initials: Z
authors.lastname: Aycan
authors.affiliation: Division of Pediatrics, Dr Sami Ulus Child Hospital, Ankara.
authors.forename: Esma
authors.initials: E
authors.lastname: Açoğlu
authors.affiliation: Division of Pediatrics, Dr Sami Ulus Child Hospital, Ankara.
authors.forename: Saliha
authors.initials: S
authors.lastname: Senel
authors.affiliation: Division of Pediatrics, Dr Sami Ulus Child Hospital, Ankara.
authors.forename: Melek Melahat
authors.initials: MM
authors.lastname: Oguz
authors.affiliation: Intergen Genetic Center, Ankara.
authors.forename: Serdar
authors.initials: S
authors.lastname: Ceylaner
mesh_terms: D002648:Child; D002675:Child, Preschool; D005260:Female; D006008:Glycogen Storage Disease / Q000175:diagnosis* / Q000201:enzymology / Q000235:genetics; D006006:Glycogen Synthase / Q000172:deficiency* / Q000235:genetics; D006801:Humans; D007223:Infant; D008099:Liver / Q000201:enzymology*; D008297:Male; D009154:Mutation / Q000235:genetics*; D010641:Phenotype; D011379:Prognosis
chemical_list: D006006:Glycogen Synthase
keywords: children; glycogen synthase deficiency; variable phenotype