title: Severe Hyperinsulinaemic Hypoglycaemia in Beckwith-Wiedemann Syndrome due to Paternal Uniparental Disomy of 11p15.5 Managed with Sirolimus Therapy.
abstract: BACKGROUND
  Almost half of the children with Beckwith-Wiedemann syndrome (BWS) will develop hyperinsulinaemic hypoglycaemia (HH). In the majority of BWS cases, HH will be transient; however, approximately in 5% of them, HH will be severe and often medically-unresponsive. Children with BWS due to paternal uniparental disomy (UPD) of chromosome 11p15 belong to this severe category and have traditionally required near-total pancreatectomy. The use of mTOR inhibitors had not been reported yet in this type of patients.
  
  
  METHODS
  A 1-month-old female with genetically confirmed BWS due to UPD of chromosome 11p15 was admitted for management of severe HH. Blood glucose concentrations were stabilised with high intravenous dextrose concentration, glucagon and octreotide infusions as she was proven to be diazoxide unresponsive. To avoid a subtotal pancreatectomy, an mTOR inhibitor - sirolimus - was introduced. The dose of sirolimus was optimised progressively and she was able to come off intravenous fluids and glucagon therapy. She has not presented any side effects and her growth is normal after 19 months of therapy.
  
  
  CONCLUSIONS
  This is the first case reported of BWS due to UPD of chromosome 11p15 where sirolimus treatment has been effective in stabilising the blood glucose concentrations and avoiding a near-total pancreatectomy without major side effects detected.
authors: Developmental Endocrinology Research Group, Clinical and Molecular Genetics Unit, Institute of Child Health, University College London, London, UK.
authors: Maria
authors: M
authors: Güemes
authors: Pratik
authors: P
authors: Shah
authors: Klára
authors: K
authors: Roženková
authors: Clare
authors: C
authors: Gilbert
authors: Kate
authors: K
authors: Morgan
authors: Khalid
authors: K
authors: Hussain
mesh_terms: D001506:Beckwith-Wiedemann Syndrome / Q000097:blood / Q000188:drug therapy / Q000235:genetics; D002880:Chromosomes, Human, Pair 11 / Q000235:genetics*; D044903:Congenital Hyperinsulinism / Q000097:blood / Q000188:drug therapy / Q000235:genetics; D005260:Female; D006801:Humans; D007223:Infant; D020123:Sirolimus / Q000008:administration & dosage*; D024182:Uniparental Disomy / Q000187:drug effects / Q000235:genetics
chemical_list: D020123:Sirolimus