ESPE Abstracts (2016) 86 P-P1-691

Neonatal Diabetes and Congenital Hypothyroidism, a Rare Condition: Report of 2 Cases with Different Genetic Causes

Carolina Mendozaa, Carolina Garfiasa, Cristian Seiltgensa, Ricardo Silvab, Isabel Hodgsona, Francisca Ugarted, Sarah Flanaganc, Sian Ellardc & Hernan Garciaa

aPontificia Universidad Catolica De Chile, Santiago, Chile; bClinica Santa Maria, Santiago, Chile; cLaboratory of Molecular Genetics, University of Exeter Medical School, Exeter, UK; dClinica Universidad De Los Andes, Santiago, Chile

Background: Neonatal diabetes (ND) is a rare monogenic form of diabetes presenting within the first six months of life. The most frequent causes include mutations in KCNJ11, ABCC8 and insulin genes, but up to 40% of patients remain without a molecular genetic diagnosis.

Case presentation: Case 1: a female newborn of non-consanguineous parents, born at 35 weeks, SGA. She presented with hyperglycemia at second day of life and low serum C-peptide 0.1 ng/ml (0.80–4.20); diabetes related autoantibodies were not performed. Congenital hypothyroidism was diagnosed at 10th day of life, thyroid ultrasound revealed severe thyroid hypoplasia and thyroid scintigraphy showed no ectopic or normotopic uptake of radiotracer. She also developed persistent diarrhea and cholestasic jaundice, with normal liver and pancreas on abdominal ultrasound. The patient died at 6 months of life due to persistent pulmonary hypertension after a severe pneumonia. Case 2: A 13 years old female, born full term but SGA. She presented with hyperglycemia since first day of life. Congenital hypothyroidism with a normal thyroid ultrasound was confirmed during first week of life. Abdominal ultrasound showed pancreatic agenesis. Nowadays she has normal growth and development. In both cases mutations in KCNJ11, ABCC8 and INS genes were excluded, sequence analysis identified a novel de novo heterozygous STAT3 missense mutation, c.1928A>G, p.Gln643Arg (case 1) and a heterozygous mutation GATA6 c.1339C>T, p.Cys447Arg (case 2). Molecular genetics laboratory, Exeter University, UK.

Conclusion: We present two cases of neonatal diabetes associated with congenital hypothyroidism. GATA6 mutation is a known cause of ND due to pancreatic agenesis associated with congenital hypothyroidism. Mutations in STAT3 have been recently associated with early-onset autoimmune disease including enteropathy, primary hypothyroidism, fibrotic lung disease, juvenile arthritis and ND. A specific molecular diagnosis has important clinical consequences as it may influence diabetes treatment and define prognosis.