ESPE Abstracts (2018) 89 P-P2-076

Novel Gata6-Mutation in a Boy with Neonatal Diabetes and Diaphragmatic Hernia

Odile Christin Gaisla, Daniel Konrada, Katharina Steindlb & Mariarosaria Lang-Muritanoa

aDepartment of Pediatric Endocrinology and Diabetology, and Children’s Research Centre, University Children’s Hospital, Zurich, Switzerland; bInstitute of Medical Genetics, University of Zurich, Zurich, Switzerland

Background: Onset of diabetes in the neonatal period with additional malformations e.g. congenital heart defects should always be suspicious for an underlying genetic disorder. For example, GATA6-mutations were identified in children with congenital heart defects and neonatal diabetes. The latter may be due to pancreas agenesis. Herein we present a novel GATA6-mutation in a boy with transient neonatal diabetes, diaphragmatic hernia, congenital heart defect and early onset scoliosis.

Case study: A term-born boy developed severe hyperglycemia with blood glucose levels up to 100 mmol/l within the first day of life. He was treated with intravenous insulin normalizing blood glucose levels. Diabetes resolved after 5 days and insulin supplementation could be stopped. In addition to diabetes, the boy presented with congenital heart defects (high grad stenosis of the left pulmonary artery, ventricular septal defect, persistent ductus arteriosus, atrial septum secundum defect), a diaphragmatic hernia and an early onset scoliosis. At the age of three years, a random evaluation revealed an HbA1c-level of 7.8% without any diabetes-related symptoms. Autoantibodies to insulin, glutamic acid decarboxylase, beta islet cells and zinc transporter-8 were negative. He was started on single insulin injection with degludec 2.5 IE and a loosened food diet without strict counting of carbohydrates. Under such regimen, HbA1c-value decreased to 6.7%. His mother presented with an autoantibody-negative diabetes at the age of 25 years and had a history of a congenital heart defect. The clinical features of our patient mirroring his mother’s medical history ultimately strengthened the suspicion of an underlying genetic disorder. Accordingly, identical heterozygous GATA6-gene mutation (c.1291C>T p.(Gln431*)) was identified in both, patient and mother. Such mutation results in an early stop-codon, presumably leading to an incomplete function of the allele’s product. To the best of our knowledge, this mutation has not been described so far in the literature. However, GATA6 mutations were previously described in patients with diabetes and congenital heart defects. Finally, aggravation of the boy’s symptoms in comparison to his mother (i.e. earlier diabetes onset, absence of diaphragmatic hernia in the mother) anticipation may be postulated.

Conclusions: A GATA6 mutation must be considered in children with neonatal diabetes and associated congenital heart defects and potentially other malformations. Anticipation and aggravation to the next generation may occur.

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