O-09 A rare cause of acute pancreatitis: Werner Syndrome

Abstract

Introduction

Lipodystrophies are rare disorders characterized by loss of body fat resulting in leptin deficiency. Patients are predisposed to metabolic complications such as severe insulin resistance, hypertriglyceridemia, and hepatic steatosis. Werner syndrome (WS) is among the progeroid syndromes in the classification of lipodystrophy. Due to its extremely rare occurrence, it can often be overlooked by the clinician.

Clinical Case

A 19 years old male patient hospitalized for non-biliary acute pancreatitis was consulted for hypertriglyceridemia and hyperglycemia. He had no history of any disease or medication use. His sister was diagnosed with type 2 diabetes mellitus at age 29. She was using linagliptin and gliclazide for 3 years. She had short stature (147 cm) and low body weight (40 kg) and had scleroderma-like skin findings. The patient also had short stature (157 cm) and low body weight (41 kg). He had scleroderma-like skin findings and generalized loss of subcutaneous adipose tissue. The laboratory results were; glucose, 261 mg/dl; creatinine, 0.46 mg/dl; ALT, 24 U/l; lipase, 161 U/l; HbA1c, 9.6%; triglyceride, 799 mg/dl; HDL, 9.6 mg/dl; LDL, 75 mg/dl; c-peptide, 4.3 ng/dl. The thyroid function test results (TSH: 29.7 µIU/ml, fT4: 6.81 pmol/L, Anti-TPO: negative) were consistent with primary hypothyroidism. Hepatosteatosis was observed in abdominal ultrasonography. We initiated intensive insulin, metformin as well as fenofibrate and levothyroxine treatment. The patient needed high insulin doses (60 IU/day). Measured serum leptin levels were found to be low (2.11 ng/ml) in suspicion of lipodystrophy. Genetic analysis of the patient and his sister showed homozygous mutation in the WRN gene (c.1105C>T p.Arg369Ter, Homozygous) which was compatible with WS. The patient was started on leptin analog therapy in a clinical trial.

Conclusion

WS is an exceptionally rare autosomal recessive genetic disorder characterized by premature aging and multisystemic complications. The clinical features encompass scleroderma-like skin changes, short stature, low body weight, alopecia, cataracts, osteoporosis, and a propensity for atherosclerotic complications and malignancies. Impaired glucose tolerance is reported in 15%–20% of WS subjects, diabetes mellitus in 55%–70%, and dyslipidemia in 60%–85%. The presence of hypertriglyceridemia, diabetes mellıtus and generalized lack of subcutaneous adipose tissue led us to suspect from lipodystrophy. Although acute pancreatitis due to hypertriglyceridemia can be seen in lipodystrophy (15-20%), first presentation of WS presenting with acute pancreatitis is very rare in the literature. The most common mutation in non-Japanese patients in WRN gene is c.1105 C>T (18.6%). Metreleptin, an analog of human leptin, is shown to ameliorate the metabolic derangements. WS remains a diagnostic challenge due to its rarity, atypical presentation, and should be kept in mind in patients with severe dyslipidemia and insulin resistance.