title: Two unrelated Chinese patients with hyperinsulinism /hyperammonemia (HI/HA) syndrome due to mutations in glutamate dehydrogenase gene.
abstract: BACKGROUND
  Hyperinsulinism/ hyperammonemia (HI/HA) syndrome is caused by excessive activity of glutamate dehydrogenase (GDH) encoded by GLUD1 gene, which oxidizes glutamate to alpha-ketoglutarate and which is a potential regulator of insulin secretion in pancreatic beta cells and of ureagenesis in the liver. So GDH is important in normal glucose homeostasis. Mutations of GDH result in HI/ HA syndrome.
  
  
  METHODS
  We have performed protein (leucine) and fat loading test on one patient. We detected the level of serum glucose, insulin and blood ammonia. Genomic DNA of the two patients and their parents is isolated from blood and the exons of GLUD1 gene are amplified by polymerase chain reaction (PCR) for direct sequencing.
  
  
  RESULTS
  The leucine diet can evocate hypoglycemia obviously. Two heterozygous mutations c.978G>A (R269H) and c.1506C>T (S445L) are identified, respectively. These are both de novo. For one patient, a better blood glucose level can be gained from leucine-restriction diet, and without diazoxide while, for the other patient, diazoxide is necessary.
  
  
  CONCLUSIONS
  The heterozygous mutations in GLUD1 gene can cause HI/HA syndrome, it is sensitive to the leucine. The diazoxide and leucine-restriction diet do well in controlling the blood glucose level.
authors.affiliation: Key Laboratory of Endocrinology, Ministry of Health, Department of Endocrinology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.
authors.forename: Chengming
authors.initials: C
authors.lastname: Diao
authors.forename: Shi
authors.initials: S
authors.lastname: Chen
authors.forename: Xinhua
authors.initials: X
authors.lastname: Xiao
authors.forename: Tong
authors.initials: T
authors.lastname: Wang
authors.forename: Xiaofang
authors.initials: X
authors.lastname: Sun
authors.forename: Ou
authors.initials: O
authors.lastname: Wang
authors.forename: Hongmei
authors.initials: H
authors.lastname: Song
authors.forename: Yun
authors.initials: Y
authors.lastname: Zhang
authors.forename: Miao
authors.initials: M
authors.lastname: Yu
authors.forename: Qian
authors.initials: Q
authors.lastname: Zhang
authors.forename: Heng
authors.initials: H
authors.lastname: Wang
mesh_terms: D001786:Blood Glucose / Q000032:analysis; D002648:Child; D005969:Glutamate Dehydrogenase / Q000235:genetics*; D006801:Humans; D022124:Hyperammonemia / Q000097:blood / Q000235:genetics*; D006946:Hyperinsulinism / Q000097:blood / Q000235:genetics*; D007223:Infant; D008297:Male; D009154:Mutation
chemical_list: D001786:Blood Glucose; D005969:Glutamate Dehydrogenase