Endocrine Abstracts

Introduction: As the prevalence of obesity increases, incidence of childhood onset type 2 diabetes mellitus (T2DM) has significantly risen, most children having a family member with T2DM. Acanthosis nigricans, marker of insulin resistance, is often noted on presentation. We describe a case of early-onset severe acanthosis nigricans and T2DM in a lean Asian Bangladeshi girl with a rare progeria partial lipodystrophy disorder, highlighting the benefit of genetic testing in unusual cases.

Case: 11.4 years old girl was reviewed for severe acanthosis nigricans present since 5.5 years-age. There was a strong family history of T2DM present in her mother, father and maternal grandmother. Parents were non consanguineous. On examination, she had normal growth parameters with height 137.5 cm (-1.09 SDS), weight 32.9 kg (-0.72 SDS) and BMI of 17.4 (-0.16 SDS). Widespread severe acanthosis nigricans, more marked on her face, neck, and skin folds. She had a long narrow face, mild truncal adiposity, thin hair, slender arms and legs. Investigations showed a normal HbA1c 29 mmol/mol (<48), fasting random glucose (BGL) 3.9 mmol/l (3.5-11) with high insulin 63.6 mU/l (2.6-24.9). Baseline pituitary bloods were pubertal and normal. An oral glucose tolerance test confirmed T2DM with fasting glucose 5 mmol/l (<7) and insulin 113mU/at 0min, rising to glucose 13.4 mmol/l (<7.8) and insulin >1000mU/l at 120min. Prolonged OGTT identified dumping syndrome at 270mins with symptomatic hypoglycaemia to 2.5 mmol/l, with insulin 336mU/l, and poor ketogenic response. Diabetes antibodies were negative. Dyslipidaemia, was present with low HDL- 1.0 mmol/l (1.2-1.7) and fatty liver was identified on ultrasound. Due to her slender habitus, MODY genetic testing was requested which showed homozygosity for a pathogenic WRN frameshift variant which had previously been reported only in trans, confirming Werner Syndrome (WS).

Conclusion: Werner syndrome (WS) is an autosomal recessive, adult-onset segmental progeria syndrome with highest incidence at approx. 1:40,000 in Japan. Cardinal features include bilateral cataracts, premature scalp hair thinning, short stature and characteristic skin lesions. T2DM is present in 71% and there is high risk of neoplasms. Early identification is important in establishing preventative and screening health management. This case highlights the value of MODY genetic testing in unusual presentations of T2DM.