Hypercalcemia in Patients with Williams-Beuren Syndrome

• Published in: The Journal of pediatrics Vol. 178; pp. 254 - 260.e4
• Main Authors: Sindhar, Sampat, BS, Lugo, Michael, BS, Levin, Mark D., MD, Danback, Joshua R., BS, Brink, Benjamin D., MS, Yu, Eric, BA, Dietzen, Dennis J., PhD, Clark, Amy L., DO, Purgert, Carolyn A., MD, PhD, Waxler, Jessica L., MS, Elder, Robert W., MD, Pober, Barbara R., MD, Kozel, Beth A., MD, PhD
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.11.2016
• Subjects: Adolescent; Adult; Aged; calcium; Calcium - blood; Child; Child, Preschool; Female; Humans; Hypercalcemia - complications; Hypercalcemia - epidemiology; Infant; Male; Middle Aged; not in the title: QTc; pediatric reference intervals; Pediatrics; Retrospective Studies; Williams Syndrome - complications; Young Adult; RR; Recommended daily intake; pediatric reference intervals; Upper limit of normal; Cr; WUSM; GFR; RDI; ULN; Supravalvar aortic stenosis; SLCH; BUN; Washington University School of Medicine; not in the title: QTc; Creatinine; Corrected QT interval; QTc; calcium; ECG; WBS; Ekectrocardiography; Glomerular filtration rate; Relative risk; St. Louis Children's Hospital; SVAS; Williams-Beuren syndrome; Blood urea nitrogen; Ca
• ISSN: 0022-3476; 1097-6833
• DOI: 10.1016/j.jpeds.2016.08.027

Objective To evaluate the timing, trajectory, and implications of hypercalcemia in Williams-Beuren syndrome (WBS) through a multicenter retrospective study. Study design Data on plasma calcium levels from 232 subjects with WBS aged 0-67.1 years were compared with that in controls and also with available normative data. Association testing was used to identify relevant comorbidities. Results On average, individuals with WBS had higher plasma calcium levels than controls, but 86.7% of values were normal. Nonpediatric laboratories overreport hypercalcemia in small children. When pediatric reference intervals were applied, the occurrence of hypercalcemia dropped by 51% in infants and by 38% in toddlers. Across all ages, 6.1% of the subjects had actionable hypercalcemia. In children, actionable hypercalcemia was seen in those aged 5-25 months. In older individuals, actionable hypercalcemia was often secondary to another disease process. Evidence of dehydration, hypercalciuria, and nephrocalcinosis were common in both groups. Future hypercalcemia could not be reliably predicted by screening calcium levels. A subgroup analysis of 91 subjects found no associations between hypercalcemia and cardiovascular disease, gastrointestinal complaints, or renal anomalies. Analyses of electrogradiography data showed an inverse correlation of calcium concentration with corrected QT interval, but no acute life-threatening events were reported. Conclusions Actionable hypercalcemia in patients with WBS occurs infrequently. Although irritability and lethargy were commonly reported, no mortality or acute life-threatening events were associated with hypercalcemia and the only statistically associated morbidities were dehydration, hypercalciuria, and nephrocalcinosis.