Poster Presentation Australian Diabetes Society and the Australian Diabetes Educators Association Annual Scientific Meeting 2017

Novel PPARG mutation causing severe hypertriglyceridaemia and insulin resistant diabetes. (#351)

Lydia Lamb 1 , Gerry P Fegan 1 , Jonathan Beilin 1 , Damon Bell 2 3 4 , Amanda Hooper 2 4
  1. Department of Endocrinology, Fiona Stanley Hospital, Murdoch, WA, Australia
  2. Department of Clinical Biochemistry, Pathwest, Fiona Stanley Hospital, Perth, Western Australia
  3. Lipid Disorders Clinic, Cardiology Department, Royal Perth Hospital, Perth, Western Australia
  4. University of Western Australia, Perth, Western Australia

Introduction

Peroxisome proliferator-activated receptor gamma (PPARG) is a transcription factor regulating adipogenesis, lipid metabolism and insulin sensitivity. PPARG mutations have been described in association with severe insulin resistant diabetes, mature onset diabetes of the young (MODY), hypertriglyceridaemia, hypertension and familial partial lipodystrophy[1][2][3][4][5][6][7][8].

Case description

A 25-year-old female was referred to endocrinology with hyperglycaemia and hypertriglyceridaemia. GP investigations had demonstrated triglycerides of 118 mmol/L and cholesterol of 31.6 mmol/L. The patient had a 1 year history of presumed type 2 diabetes mellitus managed with diet. HbA1c was 9.6%.  Significant family history included maternal hypertension, hyperlipidaemia, gestational diabetes, and premature cardiovascular disease. Paternal history was unknown. Examination revealed a normotensive female with a BMI of 27 kg/m2 and eruptive xanthomas over both knees. There was increased abdominal and peripheral subcutaneous adipose tissue stores but no acanthosis nigricans or increase in supraclavicular or submandibular fat pads. Clinical findings were not consistent with familial partial lipodystrophy (FPL). There was no clinical or biochemical evidence of pancreatitis. Glucose was 22 mmol/L without acidosis or ketosis.

The patient was managed initially with an insulin dextrose infusion with improvement in metabolic parameters. She commenced metformin and fenofibrate but declined subcutaneous insulin therapy and discharged against medical advice.

Subsequent genetic testing demonstrated that the patient is heterozygous for a novel PPARG nonsense variant p.Gln420* (c.1258C>T) predicted to result in a truncated protein missing approximately 17% of the C-terminus.  

Conclusion

This case identified a novel PPARG gene mutation which has not previously been reported and is absent from population databases. Further evaluation of the patient is planned and PPARG agonists may be a potential treatment option6,7. Other family members may be affected and screening is indicated.