Background: Williams-Beuren syndrome (WBS) is a rare genetic disorder caused by the deletion of 26-28 genes on chromosome 7. Fifteen percent of WBS patients present with hypercalcaemia during infancy, which is generally mild and resolves spontaneously before the age of 4 years. The mechanisms underlying the transient hypercalcaemia in WBS are poorly understood.
Case: We report a case of severe symptomatic hypercalcaemia in a patient with WBS, in which treatment with mild calcium restriction, hyperhydration and repeated bisphosphonate administration only resulted in short-lasting effects. Long-term lowering of serum calcium was only achieved after reducing calcium and vitamin D intake to the bare minimum.
Conclusions: This case illustrates the potential severity of hypercalcaemia in WBS, and demonstrates that both the cause as well as the solution of this problem may be found in the intestinal absorption of calcium. We hypothesise that the phenotypical resemblance between WBS and transient idiopathic infantile hypercalcaemia can be explained by similarities in the underlying genetic defect. Patients suffering from transient infantile hypercalcaemia were recently described to have mutations in CYP24A1, the key enzyme in 1,25-dihydroxyvitamin D3 degradation. In the light of this new development we discuss the role of one of the deleted genes in WBS, Williams syndrome transcription factor (WSTF), in the etiology of hypercalcaemia in WBS.