Poster Presentation ESA-SRB-APEG-NZSE 2022

Persistent, diazoxide-unresponsive hyperinsulinaemic hypoglycaemia in a child with Trisomy 21 (#450)

Madeleine Hall 1 , Shawn Tadgell 1 , Michelle Fuery 2 , Giorgio Stefanutti 3 , Louise Conwell 1 4
  1. Department of Endocrinology and Diabetes, Queensland Children's Hospital , Brisbane, Queensland, Australia
  2. Department of Dietetics and Food Services, Queensland Children's Hospital , Brisbane, Queensland, Australia
  3. Department of Paediatric Surgery, Queensland Children's Hospital , Brisbane, Queensland, Australia
  4. Greater Brisbane Clinical School, Medical School, Faculty of Medicine, University of Queensland, Brisbane, Queensland, Australia

Hyperinsulinaemic hypoglycaemia (HI) is associated with genetic syndromes and a rare feature in aneuploidies (45,XO; mosaic Trisomy 13). The Exeter Genomics Laboratory reported higher-than-expected referrals of individuals with HI and Trisomy 21. (1) The clinical phenotype (n=11) was variable with high burden of non-genetic HI risk factors. There are single reports of Trisomy 21 with insulinoma or Beckwith-Wiedemann syndrome (BWS).  

Aim

To describe a case of persistent, diazoxide-unresponsive HI in a child with Trisomy 21.

Method

Single retrospective case report. 

Results

A female with antenatal diagnosis of Trisomy 21 was delivered at 34+4 weeks gestation due to intrauterine growth retardation.  She had postnatal CMV infection, congenital hypothyroidism and a perimembranous ventriculoseptal defect (repaired at 3 months). She was dependent on gastrostomy feeds (continuous/bolus) until surgical repair of a long-gap oesphageal atresia (gastric tube with pyloroplasty) at 6 months. After a complicated peri-operative course, she progressed very slowly from gastrostomy/jejunostomy to oral feeds.

The child presented with HI at 17 months: plasma glucose 1.9mmol/L, insulin 11mU/L, low beta-hydroxy butyrate and elevated glucose infusion rate. She was unresponsive to oral Diazoxide (15mg/kg/day) and immediate-release subcutaneous Octreotide (25mcg/kg/day).

Targeted next-generation sequencing of 20 HI genes did not identify any pathogenic variants. BWS genetics was negative. 18F-DOPA PET/CT scan revealed diffuse uptake.

Safe fasting tolerance after weaning of continuous intravenous dextrose and gastrostomy feeds has been achieved with escalating monthly Lanreotide (60mg-2 months; 90mg–3 months).

Discussion

This adds to limited reports of the co-existence of HI with Trisomy 21. Other cases were perinatal, transient and not requiring diazoxide or diazoxide-responsive. Early dependence on gastrostomy and continuous/frequent feeds may have masked HI. Post-operative reduced stomach capacity and rapid gastric emptying may have contributed intermittently to ‘dumping’. Any future pancreatectomy will be complicated by past gastroesophageal surgery.  

 

  1. (1) Hewat TI et al. Pediatr Diabetes. 2022;23(4):457-461.