ESPE Abstracts (2015) 84 P-2-278

aLady Ridgeway Hospital, Colombo, Sri Lanka; bInstitute of Biomedical and Clinical Science, University of Exeter Medical School, Exeter, UK; cDevelopmental Endocrinology Research Group, Molecular Genetics Unit, Institute of Child Health, University College, London, UK

Background: Neonatal diabetes (NDM) is a rare form of monogenic diabetes which usually presents before 6 months of age. Both transient and permanent NDM have been described.

Objective: To report the molecular genetics and clinical characteristics of patients with NDM from a single centre in Sri Lanka.

Method: Retrospective analysis of clinical and molecular genetic data from patients referred to Lady Ridgeway Hospital Endocrinology unit from April 2014 to February 2015.

Results: We identified ten patients (seven male) diagnosed with permanent diabetes before the age of 9 months. Consanguinity was reported in family. Sequence analysis identified mutations in nine of the ten patients (90%) screened. Testing is currently in progress for one patient. HomozygousEIF2AK3 mutations (p.S991Nand p.L863*) were identified in two patients confirming a diagnosis of Wolcott-Rallison syndrome. Both patients had skeletal dysplasia and one patient had glucose-6-phosphatase deficiency which was diagnosed following a presentation of episodic hemolytic anaemia. One male patient, who presented with nephrotic syndrome prior to the diagnosis of NDM, had a novel hemizygousFOXP3mutation (p.E412D). In two patients a heterozygous p.R89C INS mutation was identified. Four patients were heterozygous for a K-ATP channel mutation (p.R50Q, p.R50P, p.V59M in KCNJ11andp.E208Kin ABCC8). Developmental delay was observed in two cases (p.V59M, p.R50P). Thereof these patients responded to sulphonylureas following the genetic diagnosis; the patient with the p.R50P mutation causing DEND syndrome showed no response.

Conclusions: A genetic diagnosis was possible for 90% of patients diagnosed with NDM in our cohort. Identification of a K-ATP channel mutation resulted in improved treatment for three patients highlighting the importance of genetic testing in all patients diagnosed with NDM. This is the first report of molecular genetic screening in a cohort of patients with NDM from Sri Lanka.

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