Oral Presentation Annual Meetings of the Endocrine Society of Australia and Society for Reproductive Biology and Australia and New Zealand Bone and Mineral Society 2016

Phenotypic heterogeneity in an Australian Indigenous family with monogenic diabetes due to novel mutation in ABCC8 gene (#131)

Krupali Bulsari 1 , Hang Nguyen 1 , Sridhar Chitturi 2 , Andrew Cotterill 3
  1. Royal Darwin Hospital, Casuarina, NT, Australia
  2. Department of Endocrinology, Royal Darwin Hospital, Darwin, NT, Australia
  3. Pediatric Endocrinology, Lady Cilento Children's Hospital, Brisbane, QLD, Australia

We present two cases of monogenic diabetes in Australian Indigenous siblings resulting from a novel mutation in ABCC8 gene.

Case 1 (Transient Neonatal Diabetes): 4 month old baby girl presented with febrile illness and was noted to have hyperglycaemia on admission. She was born at term with low birth weight (<3rd centile). Her postnatal course was unremarkable. Her paternal grandmother had diabetes. Investigations for genetic aetiology of neonatal diabetes were performed. She was identified to have a novel heterozygous mutation (c.2495G>C) in the highly conserved region of ABCC8 gene. She was treated with basal-bolus insulin till the age of 3 years. Following the identification of ABCC8 mutation, she was planned to transition to sulfonylurea. However, she remained euglycaemic during admission without any anti-diabetic medication. Hence, her insulin therapy was ceased and she is being monitored regularly. She remains in remission with recent HbA1c 5.8% (39mmol/mol).

Case 2 (Atypical insulin requiring diabetes): The elder sister of case 1 was diagnosed with diabetes at the age of 15 years. She had no known history of neonatal diabetes and had normal growth and development. At diagnosis, her BMI was 14.5kg/m2. She had negative antibodies for type 1 diabetes. Due to suboptimal control with metformin, she was commenced on insulin glargine. She had 2 unsuccessful pregnancies in setting of poor glycaemic control (spontaneous miscarriage in 1st trimester and intrauterine foetal death at 32 weeks). She was confirmed to have the same mutation in ABCC8 gene as her younger sibling.

Discussion: Gain of function mutations in ABCC8 gene, which codes for sulfonylurea receptor (SUR1), can cause diabetes. The case reports demonstrate the considerable phenotypic variability within the same family caused by a novel ABCC8 mutations.