Late-onset hypercalcemia in Williams-Beuren syndrome: importance of early and frequent screening and intervention

Abstract

Williams-Beuren syndrome (WBS) affects multiple systems and has a known association with infantile hypercalcemia that is typically mild and transient. We report a 12-month-old female previously diagnosed with WBS by a chromosomal microarray, who was admitted for failure to thrive. Upon evaluation, serum calcium of 19.0 mg/dL (4.75 mmol/L) (normal 9-11 mg/dL, SI: 2.25-2.75 mmol/L) and serum ionized calcium of 2.33 mmol/L (normal 1.22-1.37 mmol/L) were revealed. Her hypercalcemia correlated with symptoms of irritability, poor feeding, mild hypotonia, and constipation, which were increasingly present for 6 months prior to admission. This calcium level is one of the highest reported in association with WBS. Additionally, while hypercalcemia associated with WBS typically resolves by the first year, this case represents a later presentation as compared to other reports. The patient initially responded to conservative treatment with intravenous fluids administration, loop diuretic therapy, and dietary calcium restriction. However, she subsequently had rebound hypercalcemia 5 weeks after treatment and received one dose of intravenous bisphosphonate with subsequent resolution of her hypercalcemia. Our report highlights the importance of screening, early management, and recognition of late presentation hypercalcemia in the setting of WBS.

Endocrine dysfunctions in children with Williams-Beuren syndrome

“…Symptomatic hypercalcemia in WBS is rare, but careful monitoring and appropriate management is required in the case of severe hypercalcemia. There are some reports of rebound hypercalcemia after treatment, emphasizing the importance of re-evaluating serum calcium levels during the follow-up period 25 26) . The cases in this study were treated with conventional therapies such as intravenous fluid and diuretics.…”

Dental-craniofacial manifestation and treatment of rare diseases

“…Routine supervision of blood pressure, blood glucose and calcium levels are generally recommended for all patients with WS, surgery or stent insertion is the preferred method for moderate to severe aortic stenoses, an oral hypoglycaemic agent or insulin administration might be required for WS patients with potential diabetes mellitus, and bisphosphonate therapy is used for WS patients with significantly decreased bone density. 21,44–46 Additionally, the application of anxiolytic and antipsychotic agents is occasionally prescribed, and behavioural treatments, such as the practice of relaxation, music treatment and social skill training, might be effective to channel the nature of affected patients. 47 Other treatments, including dental restoration and orthodontic treatments, are administered depending on the patient's particular symptoms, and an early dental evaluation and dietary counselling are necessary to determine the presence of dental anomalies, such as caries and enamel structural defects.…”

Oral prednisolone for management of persistent hypercalcemia afterhypercalcemic crisis in the Williams-Beuren syndrome

“…However, actionable hypercalcemia occurs infrequently and usually shows a bimodal age distribution: infancy and adolescence, or adulthood [4]. Although hypercalcemia is generally considered transient during infancy, it may last for several months and result in significant morbidity [4,6]. The usual consequences of hypercalcemia such as dehydration, irritability, decreased oral intake, polyuria and polydipsia result in failure to thrive and contribute to an already compromised growth in WBS [4].…”

“…Although patients in the hypercalcemic crises seem to respond well to several calcium lowering drugs, a long-term use of these agents is generally avoided [4,10]. A closely supervised reduction in the intakes of calcium and vitamin D as well as free water intake may lower serum calcium levels in most but not all patients with WBS [6,11]. Considering that our patient exhibited severe growth failure, nephrocalcinosis and the recurrence of hypercalcemia, we aimed to treat him with steroid therapy which had previously been used to treat acute hypercalcemia in WBS as well as chronic hypercalcemia due to other conditions in children [4].…”

“…The management of acute severe hypercalcemia usually involves initial treatment using hyperhydration and loop diuretics, and steroids, calcitonin, bisphosphonates and dialysis if serum calcium concentrations fail to drop [4,5]. With the treatment of acute hypercalcemic episode, the serum calcium levels usually remain below the actionable range but some patients may suffer from recurrences and chronic hypercalcemia [4,6]. There is scarce information on the treatment of chronic hypercalcemia in WBS although most patients are managed with restriction of dietary calcium and vitamin D intake below the recommended daily intake (RDI) similar to other disorders with the risk of hypercalcemia with RDI doses of calcium and vitamin D [7].…”