title: Rapid genetic analysis in congenital hyperinsulinism.
abstract: BACKGROUND
  In severe, medically unresponsive congenital hyperinsulinism (CHI), the histological differentiation of focal versus diffuse disease is vital, since the surgical management is completely different. Genetic analysis may help in the differential diagnosis, as focal CHI is associated with a paternal germline ABCC8 or KCNJ11 mutation and a focal loss of maternal chromosome 11p15, whereas a maternal mutation, or homozygous/compound heterozygous ABCC8 and KCNJ11 mutations predict diffuse-type disease. However, genotyping usually takes too long to be helpful in the absence of a founder mutation.
  
  
  METHODS
  In 4 patients, a rapid genetic analysis of the ABBC8 and KCNJ11 genes was performed within 2 weeks on request prior to the decision of pancreatic surgery.
  
  
  RESULTS
  Two patients had no mutations, rendering the genetic analysis non-informative. Peroperative multiple biopsies showed diffuse disease. One patient had a paternal KCNJ11 mutation and focal disease confirmed by positron emission tomography scan and biopsies. One patient had a de novo heterozygous ABBC8 mutation and unexplained diffuse disease confirmed by positron emission tomography scan and biopsies.
  
  
  CONCLUSIONS
  A rapid analysis of the entire ABBC8 and KCNJ11 genes should not stand alone in the preoperative assessment of patients with CHI, except for the case of maternal, or homozygous/compound heterozygous disease-causing mutations.
authors.affiliation: Department of Paediatrics, Odense University Hospital, Odense, Denmark.
authors.forename: Henrik B T
authors.initials: HB
authors.lastname: Christesen
authors.forename: Klaus
authors.initials: K
authors.lastname: Brusgaard
authors.forename: Jan
authors.initials: J
authors.lastname: Alm
authors.forename: Sture
authors.initials: S
authors.lastname: Sjöblad
authors.forename: Khalid
authors.initials: K
authors.lastname: Hussain
authors.forename: Claus
authors.initials: C
authors.lastname: Fenger
authors.forename: Lars
authors.initials: L
authors.lastname: Rasmussen
authors.forename: Claus
authors.initials: C
authors.lastname: Hovendal
authors.forename: Timo
authors.initials: T
authors.lastname: Otonkoski
authors.forename: Bendt Brock
authors.initials: BB
authors.lastname: Jacobsen
mesh_terms: D018528:ATP-Binding Cassette Transporters / Q000235:genetics; D044903:Congenital Hyperinsulinism / Q000175:diagnosis* / Q000235:genetics* / Q000601:surgery; D003937:Diagnosis, Differential; D005820:Genetic Testing / Q000379:methods*; D005838:Genotype; D006801:Humans; D007231:Infant, Newborn; D009154:Mutation; D010641:Phenotype; D015221:Potassium Channels / Q000235:genetics; D024661:Potassium Channels, Inwardly Rectifying / Q000235:genetics; D011300:Preoperative Care; D011955:Receptors, Drug / Q000235:genetics; D064233:Sulfonylurea Receptors; D000099161:Kcnj11 Channel
chemical_list: D018528:ATP-Binding Cassette Transporters; D015221:Potassium Channels; D024661:Potassium Channels, Inwardly Rectifying; D011955:Receptors, Drug; D064233:Sulfonylurea Receptors; D000099161:Kcnj11 Channel