ESPE Abstracts (2019) 92 P1-27

A Case of Neonatal Diabetes with Hyperferritinemia: A Distal PTF1A Enhancer Mutation

Gülçin Arslan1, Sezer ACAR1, Özlem Nalbantoğlu1, Özge Köprülü1, Beyhan Özkaya1, Elisa De Franco2, Sian Ellard2, Behzat Özkan1

1Division of Pediatric Endocrinology, Health Sciences University, Dr. Behcet Uz Child Disease and Pediatric Surgery Training and Research Hospital, Izmir, Turkey. 2Department of Molecular Genetics, Institute of Biomedical and Clinical Science, University of Exeter Medical School, Exeter, United Kingdom

Introduction: Neonatal diabetes, defined as the onset of diabetes within the first six months of life, is very rare disease. Several genetic factors caused to neonatal disease have been identified to date. PTF1A (pancreatic transcription factor 1a) play a key role in early pancreas development and cerebellar neurogenesis. Biallelic mutations in PTF1A have been reported in patients with pancreatic and cerebellar agenesis, whereas mutations located in a distal pancreatic-specific enhancer cause isolated pancreatic agenesis. In here, we present a case with neonatal diabetes, high ferritin level, and cholestasis and who has initially been misdiagnosed as hemochromatosis. Following further genetic analysis, distal PTF1A enhancer mutation have been identified.

Case: Two and half month male was referred to our hospital from another center because of hyperglycemia and cholestasis. He was born with a birth weight of 1830 gr at 36 gestational week from mother with oligohydramnios. The parents were relatives (first-degree-cousin). On physical examination, his weight was 1900 gr (<3p), height was 44 cm (<3p) and low ear, triangle face and micrognathia were observed. Both of testes were in scrotum (2/2 cc). In the laboratory, glucose 327 mg/dL, insulin 0.4 µU/mL (2.6–24.9), c-peptide < 0.1 ng/mL (0.9–7.1), urine and blood ketones were negative, ammonia and lactate were normal, ferritin was 3057.58 ng/ml (50–200). Insulin infusion was initially started. Sequencing analyzes of ABCC8/KCNJ11 were planned and glibenclamide was added. Because of persistent hyperferritinemia, abdominal MRI was performed and it was showed increased intensity in the liver, which is suggesting hemochromatosis. Therefore, HFE gene analysis was performed. In order to show tissue iron deposition, buccal biopsy was performed; however biopsy specimen was inadequate. Pump treatment was unsuccessful because of technical problems. NPH was added and normoglycemia was achieved. No mutation in ABCC8/KCNJ11 was found; therefore, glibenclamide treatment was stopped. Because of inadequate weight gain and steatocrit in skool, pancreatic enzyme replacement was started. Analysis of HFE gene revealed no mutation and during the treatment, normal serum ferritin levels were achieved. Following further genetic analysis, a distal PTF1A enhancer homozygous mutation (g.23508336 G>T) was found. His mother and father were heterozygous for the same mutation.

Conclusion: Hyperferritinemia can be accompanied in cases with neonatal diabetes as an acute phase reactant. If no mutation is detected in ABCC8 and KCNJ11 in cases of neonatal diabetes, investigation of rare genetic causes should be kept in mind.

Keywords: Neonatal diabetes, PTF1A mutation, hyperferritinemia

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