title: A Case Series: Congenital Hyperinsulinism.
abstract: BACKGROUND
  Congenital hyperinsulinism is a rare inherited disease caused by mutations in genes responsible for β-cell's function in glucose hemostasis leading to profound and recurrent hypoglycemia. The incidence of the disease is about 1 in 50000 newborns. Mutations in at least 8 genes have been reported to cause congenital hyperinsulinism. Mutations in ABCC8 gene are the most common cause of the disease that account for approximately 40% of cases. Less frequently KCNJ11 gene mutations are responsible for the disease. Mutations in other genes such as HADH account for smaller fractions of cases. In nearly half of the cases the cause remains unknown.
  
  
  METHODS
  During the period between 2005 and 2010, a total of six patients with persistent hyperinsulinism were investigated at Mofid Children's Hospital. In this study all of the patients had early onset hyperinsulinemia. Five patients had consanguineous parents. After failure of medical treatment in three patients, They were undergone pancreatectomy. Two diffuse types and one focal type had been recognized in pathological analysis of intra-operative frozen specimens of pancreas in these patients. Genetic analysis was performed using polymerase chain reaction followed by Sanger sequencing for ABCC8, KCNJ11and HADH genes. In five patients homozygous mutations in these genes were identified that indicated an autosomal recessive pattern of inheritance. In one patient a heterozygous mutation in ABCC8 was identified, indicating possible autosomal dominant inheritance of the disease.
  
  
  CONCLUSIONS
  Congenital hyperinsulinism can have different inheritance pattern. Autosomal recessive inheritance is more common but less frequently autosomal dominant inheritance can be seen. It appears that mutations in ABCC8 gene can show both autosomal recessive and autosomal dominant inheritance of the disease. PCR followed by Sanger sequencing proved to be an efficient method for mutation detection in three investigated genes. Despite early diagnosis, psychomotor retardation was seen in two patients.
authors.affiliation: Department of Pediatric Endocrinology, Mofid Children's Hospital, Shahid Beheshti University of Medical Sciences, Tehran, IR Iran.
authors.forename: Mohammad Reza
authors.initials: MR
authors.lastname: Alaei
authors.affiliation: Genetic Counseling Division, Mofid Children's Hospital, Shahid Beheshti University of Medical Sciences, Tehran, IR Iran.
authors.forename: Susan
authors.initials: S
authors.lastname: Akbaroghli
authors.affiliation: Department of Medical Genetics, School of Medicine, Tehran University of Medical Sciences, Tehran, IR Iran.
authors.forename: Mohammad
authors.initials: M
authors.lastname: Keramatipour
authors.affiliation: School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, IR Iran.
authors.forename: Ali
authors.initials: A
authors.lastname: Alaei
keywords: ABCC8; Congenital Hyperinsulinism; HADH; KCNJ11