Endocrine Abstracts

Advances in molecular genetics revealed various causes for neonatal diabetes (ND) Wider clinical awareness led to recognition of different phenotypes. In areas like the Gulf, it is expected that the incidence of ND to be higher due to the high frequency of consanguinity. The different ethnic background might result in different causes and phenotypes of ND compared to data reported from the west.

We report 19 patients from 11 families with ND. All patients were pancreatic autoantibody negative and 16 presented before 6 months of age. All patients were born at term and were small for gestational age. All were born to first degree relative parents. 12 patients were on multiple daily injections and seven on insulin pump therapy. Eight had liver impairment, five skeletal dysplasia and one had pancreatic agenesis. Four patients died at ages 3, 6, 7 and 15 years and one had liver failure requiring transplant.

Genetic analysis was carried out in all patients. KCNJ11, ABCC8, INS genes were sequenced in all patients while EIF2AK3, GCK, IPF1, PTF1A, GATA6, RFX6 were done based on specific clinical features.

Ten patients (five families) had Wolcott Rallison syndrome due to mutations in the EIF2AK3 gene; W430X, G956E, E524X, deletion exon 9–13, and I650T (novel). All parents were confirmed to be heterozygous carriers. Four siblings were homozygous to a novel mutation in insulin gene; INS c-331C>G. The same mutation was later found in another unrelated patient. One child had a kATP mutation and was successfully switched to sulphonyleurea and one patient had a novel heterozygous H410Y ABCC8 variant.

ND is an important cause of diabetes in areas like the Gulf countries. The main causes of ND vary in different ethnic groups. Phenotype related to age at presentation, organ involvement and disease severity may vary within the same family of affected children.

– WRS as the commonest cause of neonatal diabetes in this cohort with various ages at presentation of liver impairment.

– Death due to liver failure occurs regardless of age of presentation of liver disease.

– First patient reported to undergo liver transplant due to liver failure of WRS.

– Different phenotype and age at diabetes presentation in siblings of the same family with insulin gene mutation (6 weeks, 3 months, 13 years, 18 years).

– Relative difficulty to switch from insulin to sulphonylurea in a previously reported kATP channel mutation.