Abstract for presentation at 11th International Congress of Human Genetics

Genetic findings in Australian Patients with Persistent Hyperinsulinaemic Hypoglycaemia of Infancy (PHHI)

  • Ms Janaki Shah, Dept of Endocrinology, Mater Childrens Hospital & School of Biomolecular and Biomedical Sciences, Griffith University, Australia
  • Dr David Maguire, Australia
  • Dr David Cowley, Australia
  • Dr Ristan Greer, Department of Paediatrics and Child Health, Univeristy of Queensland, Australia
  • Dr Andrew Cotterill, Dept of Endocrinology, Mater Childrens Hospital, Australia
  • Dr Andrew Cotterill, Dept of Endocrinology, Mater Childrens Hospital, Australia

    • Persistent Hyperinsulinaemic Hypoglycaemia of Infancy (PHHI) is a disorder of unregulated insulin secretion accompanied by mild to severe hypoglycaemia. Patients usually present in the first 72 hours of life with mild to severe symptoms of hypoglycaemia. Treatment is aimed at maintaining euglycemia, and usually employs drugs such as diazoxide. Patients who fail to respond to medical treatment require a partial or sub-total pancreatectomy. Up to 50% of all patients will suffer from long term neurological impairment as a result of the hypoglycaemic episodes. The candidate genes are currently – ABCC8 and KCNJ11 that encode the K-ATP channel on beta cells, and the genes encoding the enzymes GCK, GLUD1 which play important roles in glucose metabolism. Recently, SCHAD mutations have also been reported with distinct HI phenotype.
    We have a cohort of 42 patients from Australasia diagnosed with PHHI. They have been segregated by their response to medical treatment - those who failed to respond to maximal doses of medical treatment required surgery and were assumed to have a severe form of the disease. Surgical patients were genotyped for ABCC8 and KCNJ11; genes which are usually associated with the severe form of the disease. Medical patients were genotyped for ABCC8, KCNJ11, GCK and GLUD1.
    Our genetic analysis show that 80% (16 of 20 patients) of the surgical cohort carry either novel or previously reported mutations on ABCC8, while only one (1 of 22) of the milder medical cohort carried a mutation on any of the candidate genes analysed. We believe that there maybe an alternate genetic cause of PHHI, in some of the other pathways associated with glucose sensing and the release of insulin that accounts for congenital hyperinsulinism in our patients as well as the previously reported 50% of HI patients in whom no genetic cause has been identified. Here, we propose some of the mechanisms that could account for hyperinsulinism in the patients with unknown aetiology.

    Conference Organiser - ICMS Pty Ltd