ESPE Abstracts

Background: Recently PTF1A enhancer mutations have been described in subjects with early-onset exocrine and endocrine pancreas insufficiency.

Objective: To describe the clinical course in three children with PTF1A enhancer mutations, in particular anthropometric development, insulin requirement and diabetes control.

Method: Retrospective analysis of growth, weight and BMI development as well as insulin requirement and HbA1c level in three children with mutations in the PTF1A enhancer.

Result: We report on three female siblings with a PTF1A enhancer mutation (g.23508437A>G), born to consanguineous parents. Age at onset of diabetes was at birth, at 10.6 and 7 years; all exhibited pancreas hypoplasia leading to pancreatic exocrine insufficiency, requiring pancreatic enzyme substitution. Islet cell, insulin, GAD and IA2 antibodies were negative in all. However, transglutaminase antibodies were detected in one sibling; duodenal biopsy confirmed a diagnosis of celiac disease. Regarding anthropometry, birth parameters were as follows: BW-SDS: −3.09, −1.87 and −1.92, BL-SDS: −4.0, −0.17 and −1.77; current height at 10.5, 11.8 and 18.5 years: 146.8 cm (+0.37 SDS), 167.7 cm (+1.91 SDS), 165.7 cm (−0.38), corresponding BMI: 15.1 kg/m² (−1.03), 18 kg/m² (−0.06), 18.9 kg/m² (−1.00). Insulin therapy was started at diagnosis of IDDM. Average HbA1c levels for the last 24 months were at a current age of 10.5, 11.8 and 18.5 years 7.8%, 8.0% and 8.9% respectively, with a most recent requirement of insulin 0.5, 0.32 and 0.7 IU/kg body weight. Current pancreatic enzyme substitution therapy consists of pancreatin 2000–3000 IU/g fat per day.

Conclusion: Subjects with PTF1A mutations seem to exhibit adequate anthropometric development and acceptable diabetes control under insulin and pancreatic enzyme substitution. Despite a non-immune etiology of IDDM, patients should be monitored for additional autoimmune disorders such as celiac disease, which can complicate the clinical course and affect diabetes control.