Searchable abstracts of presentations at key conferences in endocrinology
Endocrine Abstracts (2008) 16 PL5

Penisula Medical School, Exeter, UK.

Insulin is a crucial growth factor in utero as well as the key post natal determinant of blood glucose. Mutations in beta-cell genes altering insulin secretion therefore present with both altered birth weight and also hyper or hypoglycaemia. Recent advances in the genetics of neonatal diabetes and neonatal hyperinsulinism give key insights to beta-cell physiology as well as offering improved clinical management.

In the genes encoding key beta-cell proteins Kir6.2, SUR1 and glucokinase different mutations will result in both activating and inactivating mutations and result in the opposing phenotypes of hypo and hyper glycaemia. Recently, we showed mutations in HNF4alpha the same loss of function mutations result in both transient neonatal hypoglycaemia and also latter beta-cell failure and diabetes.

There have been major advances in the genetics of neonatal diabetes and a molecular genetic diagnosis is now possible most patients with transient or permanent neonatal diabetes. In transient neonatal diabetes (TNDM) is now possible to give a diagnosis in over 95% of patients. The commonest cause are abnormalities of imprinting in the region of the ZAC gene on 6q (71%) the majority of other patients either have a mutation in SUR1 (14%) or Kir6.2 (12%). KATP mutations like ZAC anomalies that cause TNDM may also relapse with permanent diabetes outside the neonatal period.

In permanent neonatal diabetes (PNDM), the commonest cause is Kir6.2 mutations (30%) but SUR1and insulin mutations that may present as dominant or recessive mutations are found in 12 and 14% of cases, respectively. Neurological features which account for approximately 20% of Kir6.2 mutations are seen in <5% in SUR1 patients and are not a feature of insulin mutations.

The major reason that genetics have been important in neonatal diabetes is because it had altered treatment. Patients with SUR1 and Kir6.2 mutations, even if insulin dependent, can improve control by replacing insulin injections with sulphonylurea tablets.

Neonatal diabetes is now an area where a molecular genetic diagnosis is not a luxury but a necessity. A molecular diagnostic service is provided by centres throughout the world including our own on and is having a positive impact on the care of patients with neonatal diabetes.

Article tools

My recent searches

No recent searches.

My recently viewed abstracts