title: Assessment of Nifedipine Therapy in Hyperinsulinemic Hypoglycemia due to Mutations in the ABCC8 Gene.
abstract: BACKGROUND
  Previous case reports have documented the effectiveness of l-type calcium channel blockers (such as nifedipine and verapamil) for treating different forms of hyperinsulinemic hypoglycemia (HH).
  
  
  OBJECTIVE
  To systematically assess the glycemic response to nifedipine therapy in 11 patients with HH due to mutations in the ABCC8 gene.
  
  
  METHODS
  Dose escalation of nifedipine therapy.
  
  
  METHODS
  Eleven children who were inpatients at a tertiary hospital and had diazoxide unresponsive HH due to mutations in the ABCC8 gene.
  
  
  METHODS
  Nifedipine was administered orally at an escalating dose up to a maximum of 2.5 mg/kg/d.
  
  
  METHODS
  Improvement in glycemic control, avoidance of hypoglycemic episodes, reduction of intravenous glucose infusion, and reduction in the requirements of other medical therapies.
  
  
  RESULTS
  The median age of the patients was 0.44 years (range 0.14 to 3.77). The ABCC8 gene mutations were homozygous in 3 cases, paternally inherited heterozygous in 4, and compound heterozygous in 4. 18F-DOPA PET/CT scan demonstrated a focal lesion in 2 cases and the rest were diffuse HH disease. One subject had nifedipine as monotherapy, whereas the rest had it in combination with octreotide/glucagon/diazoxide or cornstarch. After a median of 6.5 (3 to 23) days of maximal (2.5 mg/kg/d) dose of nifedipine therapy, none of the patients showed any improvement in glycemic control and patients continued to have hypoglycemic episodes.
  
  
  CONCLUSIONS
  HH due to mutations in the ABCC8 gene does not respond to nifedipine therapy. Mutations in the KATP channel genes might render the l-type calcium channel ineffective to therapy with nifedipine.
authors.affiliation: Genetics and Genomic Medicine Programme, Genetics and Epigenetics in Health and Disease Section, Institute of Child Health, University College London, London WC1N 1EH, United Kingdom.|Endocrinology Department, Great Ormond Street Hospital for Children National Health Service Trust, London WC1N 1EH, United Kingdom; and.
authors.forename: Maria
authors.initials: M
authors.lastname: Güemes
authors.affiliation: Endocrinology Department, Great Ormond Street Hospital for Children National Health Service Trust, London WC1N 1EH, United Kingdom; and.
authors.forename: Pratik
authors.initials: P
authors.lastname: Shah
authors.affiliation: Endocrinology Department, Great Ormond Street Hospital for Children National Health Service Trust, London WC1N 1EH, United Kingdom; and.
authors.forename: Shavel
authors.initials: S
authors.lastname: Silvera
authors.affiliation: Endocrinology Department, Great Ormond Street Hospital for Children National Health Service Trust, London WC1N 1EH, United Kingdom; and.
authors.forename: Kate
authors.initials: K
authors.lastname: Morgan
authors.affiliation: Endocrinology Department, Great Ormond Street Hospital for Children National Health Service Trust, London WC1N 1EH, United Kingdom; and.
authors.forename: Clare
authors.initials: C
authors.lastname: Gilbert
authors.affiliation: Endocrinology Department, Great Ormond Street Hospital for Children National Health Service Trust, London WC1N 1EH, United Kingdom; and.
authors.forename: Louise
authors.initials: L
authors.lastname: Hinchey
authors.affiliation: Genetics and Genomic Medicine Programme, Genetics and Epigenetics in Health and Disease Section, Institute of Child Health, University College London, London WC1N 1EH, United Kingdom.|Department of Pediatric Medicine, Sidra Medical and Research Center, Doha, Qatar.
authors.forename: Khalid
authors.initials: K
authors.lastname: Hussain
mesh_terms: D002121:Calcium Channel Blockers / Q000627:therapeutic use*; D002675:Child, Preschool; D015331:Cohort Studies; D044903:Congenital Hyperinsulinism / Q000188:drug therapy* / Q000235:genetics; D003981:Diazoxide / Q000627:therapeutic use; D004359:Drug Therapy, Combination; D005260:Female; D005765:Gastrointestinal Agents / Q000627:therapeutic use; D005934:Glucagon / Q000627:therapeutic use; D006801:Humans; D007223:Infant; D008297:Male; D009543:Nifedipine / Q000627:therapeutic use*; D015282:Octreotide / Q000627:therapeutic use; D011446:Prospective Studies; D013213:Starch / Q000627:therapeutic use; D064233:Sulfonylurea Receptors / Q000235:genetics; D016896:Treatment Outcome
chemical_list: C577507:ABCC8 protein, human; D002121:Calcium Channel Blockers; D005765:Gastrointestinal Agents; D064233:Sulfonylurea Receptors; D013213:Starch; D005934:Glucagon; D009543:Nifedipine; D003981:Diazoxide; D015282:Octreotide