title: Hyperinsulinemic hypoglycemia: think of hyperinsulinism/hyperammonemia (HI/HA) syndrome caused by mutations in the GLUD1 gene.
abstract: BACKGROUND
  Hyperinsulinism-hyperammonemia syndrome (HI/HA) is a rare autosomal dominant disorder presenting with hypoglycemia and hyperammonemia. It is caused by activating mutations in the GLUD1 gene.
  
  
  METHODS
  Three patients from two different centers, a 14-month-old female, a 28-year-old female (mother of the first patient) from Toronto and an unrelated 2.5-year-old male from Vienna, presented with multiple episodes of seizures associated with hypoglycemia.
  
  
  RESULTS
  All patients had mild to moderate hypoglycemia, inappropriate insulin levels and mild hyperammonemia, thus suggesting a disorder of glutamate dehydrogenase (GDH). Molecular genetic testing of the GLUD1 gene identified heterozygous mutations in all patients (patient 1 and her mother a novel c.1526G>C mutation; patient 3 a known c.809C>G mutation).
  
  
  CONCLUSIONS
  We present three new patients with GDH caused by heterozygous mutation in the GLUD1 gene. Mild hyperammonemia and inappropriately elevated insulin levels should suggest a GLUD1 mutation. Early onset hypoglycemia associated with seizures, and especially a good response to diazoxide treatment, should include this disorder in the differential diagnosis of hyperinsulinemic hypoglycemia.
authors.forename: Christel
authors.initials: C
authors.lastname: Tran
authors.forename: Vassiliky
authors.initials: V
authors.lastname: Konstantopoulou
authors.forename: Michelle
authors.initials: M
authors.lastname: Mecjia
authors.forename: Kusiel
authors.initials: K
authors.lastname: Perlman
authors.forename: Saadet
authors.initials: S
authors.lastname: Mercimek-Mahmutoglu
authors.forename: Jonathan B
authors.initials: JB
authors.lastname: Kronick
mesh_terms: D000328:Adult; D002675:Child, Preschool; D005260:Female; D005969:Glutamate Dehydrogenase / Q000235:genetics*; D006801:Humans; D022124:Hyperammonemia / Q000150:complications / Q000235:genetics* / Q000473:pathology; D006946:Hyperinsulinism / Q000150:complications / Q000235:genetics* / Q000473:pathology; D007003:Hypoglycemia / Q000150:complications / Q000235:genetics* / Q000473:pathology; D007223:Infant; D008297:Male; D009035:Mothers; D009154:Mutation / Q000235:genetics*; D011379:Prognosis; D012640:Seizures / Q000175:diagnosis / Q000209:etiology; D013577:Syndrome
chemical_list: D005969:Glutamate Dehydrogenase; C561840:GLUD1 protein, human