Endocrine Abstracts

Introduction: Williams syndrome (WS) is a multi-systemic disorder caused by a deletion in the region 7q11.23. Childhood endocrine follow-up is mainly aimed to monitor hypercalcemia and thyroid function. A high prevalence (63–71%) of impaired glucose tolerance (IGT) and diabetes mellitus (DM) in young adults with WS is reported. WS guidelines recommend Oral Glucose Tolerance Test (OGTT) starting from 30 years of age. We demonstrate evidence of IGT and DM in WS at a much earlier age.

Case report: A 15.6 years old WS female presented with history of polyuria and polydipsia. She was never overweight and initially presented with glycosuria, moderate ketonuria and hyperglycaemia without acidosis, during a gastroenteritis at the age of 4.2. Subsequently diabetic ketoacidosis appeared, insulin was started but shortly stopped for persistent hypoglycaemia. Subsequent glucose monitoring was normal and remained off insulin. At the age of 10 nocturnal polyuria became evident. Glycosuria, without ketosis or hyperglycaemia, was confirmed and classified as ‘renal glycosuria’ due to WS renal impairment. Recent investigations confirmed glycosuria without ketonuria, and raised HbA1c (51 mmol/mol). OGTT confirmed DM (T₀=7.8 mmol/l; T₁₂₀=15.3 mmol/l). Insulin assessment was not available, C-peptide secretion was impaired (T₀=<0.1mmol/l; peak T₆₀=0.32 nmol/l). Autoimmunity is still pending. Type 2 like DM with β-cells impairment was considered most probable and diet modifications and Metformin treatment were started, improving glucose metabolism.

Conclusions: We describe the youngest patient with DM associated with WS. Main hypothesis for the underling etiopathogenesis suggest hyperinsulinism secondary to insulin sensitivity reduction linked to genes involved in deletion. Lack of studies in childhood raises the issue about the timing of onset of DM. It is possible that hyperinsulinism could be present for many years before IGT. Our finding demonstrates for the first time the need for studies aimed to assess the prevalence of glucose metabolism abnormalities in WS during childhood with appropriate intervention.