ESPE Abstracts

Introduction: GATA6 is a gene that encodes a zinc transcription factor with a key role in the development of several organ systems, as evidenced by the many congenital malformations that have been associated with its mutation. GATA6 plays a role in gut, lung, pituitary, and heart development, with broad expression in developing heart tissue and close link with pancreatic agenesis/hypoplasia. Most cases present with neonatal Diabetes, but a small proportion develop adolescent or adult-onset diabetes clinically distinct from type 1 or type 2 diabetes in that patients are typically young and nonobese with negative pancreatic antibodies.

Case Report: Proband is a female born to non-consanguineous parents, with truncus arteriosus requiring several cardiac surgical interventions. No hyperglycaemic episodes were recorded in the neonatal period. Diabetes was diagnosed at 14 years of age, presenting as incidental finding, not in DKA. She had a low but detectable C-peptide level at diagnosis. Pancreatic autoantibodies including zinc transport 8 were negative. Further investigations revealed a hypoplastic pancreas. Genetic testing showed a heterozygous frameshift pathogenic GATA6 mutation. Genetic testing has also been offered to patient’s mother and brother given their history of Persistent Ductus Arteriosus and Tetralogy of Fallot respectively and known autosomal dominant inheritance pattern of GATA6 mutations. Patient was initially on long-acting insulin in the evenings and short-acting insulin at mealtimes with variable blood glucose control. She has recently been started on Omnipod 5, latest Time in Range (TIR) is 61% and HbA1c is 55 mmol/mol.

Discussion: GATA6 mutations are associated with a broad spectrum of diabetes phenotypes, pancreatic dysgenesis, and a variety of congenital heart diseases. GATA6 mutation should be suspected in patients presenting with multisystem congenital disease, atypical diabetes with negative pancreatic antibodies and/or a suggestive family history. Recognition and identification of genetic diabetes may improve patient understanding and empowerment and allow for better tailored management. Identification of a genetic disorder may have important implications for family planning.