Background: Neonatal diabetes (ND) is a rare, mostly sporadic disorder diagnosed within the first 6 months of life that can either be transient or permanent. We report on a family of four phenotypically heterogenous subjects with ND characterized by a new heterozygous missense mutation (D212I) in exon 5 of the ABCC8 gene encoding the SUR1 subunit of the KATP channel.
Patients: In each of small-for-gestational-age (SGA) female monocygous twins, ND occurred at the age of 3 months requiring transient insulin therapy for 4 months. At the age of 14 years, clinical diabetes relapsed and insulin treatment had to be restarted. Both twins got one offspring, each. The daughter of the first twin was diagnosed with ND at the age of one month and treated with insulin using continuous subcutaneous insulin infusion (CSII) until 6 months with continuous remission thereafter. Learning disability was diagnosed at the age of 6 years. The son of the second twin was born with SGA and had postpartal hyperglycaemia. CSII was started at day 11 after birth. Furthermore, neurological features with motor and social development delay were present. Molecular genetic analysis was performed reveiling an identical new mutation in all subjects. After molecular diagnosis, treatment of the boy was transferred from insulin (HbA1c 5.8%) to oral sulfonylureas. Fast reduction of insulin and switch of therapy to high-dose glibenclamide was done for the first time completely under ambulatory conditions using real-time continuous glucose monitoring. Metabolic control improved (HbA1c 5.3%) and glycaemic fluctuations as well as frequency of hypoglycaemia decreased significantly. Both mothers were sucessfully transferred to glibenclamide as well.
Summary: In this family, a rare genetic form of neonatal diabetes with neurological development delay and heterogenous genotype-phenotype correlation occurred in combination with a primarily described SUR 1-mutation.
03 - 07 May 2008
European Society of Endocrinology