LAUSR

Abstract Background: Williams-Beuren Syndrome (WBS) is due to a microdeletion on chromosome 7q11, and is associated with facial dysmorphisms, supravalvular aortic stenosis, a sociable personality and infantile hypercalcemia that is clasically mild and transient. Here we describe an infant found to have incidental severe hypercalcemia that led to a diagnosis of WBS. Case: A 9 month old girl, born at 36 weeks, developed failure to thrive (FTT) thought to be due to poor appetite. She failed to gain weight despite fortification of formula to 24 kcal/oz three months ago. Her medical history included delayed motor milestones, transverse hypoplastic aortic arch, persistent pulmonary stenosis and constipation managed with prune juice. On exam, heart rate was 134 bpm, BP 100/48 (>95th%ile for height). Her weight was 5.9 kg (<1st%ile) and length 66.4 cm (3rd%ile). She was noted to have facial dysmorphisms (stellate iris, epicanthal folds, broad nasal tip, long philtrum, thick vermilion of upper lip, and micrognathia). She was able to sit briefly without support, and was generally hypotonic. She also had a grade II murmur at the left lower sternal border (LLSB). Due to persistent FTT, labs were obtained and showed serum calcium (Ca) of 17.3 mg/dL (9.0-11.0), which was repeated and was 18.6 mg/dL, prompting admission. On admission: iCa 2.60 mmol/L (1.08-1.30), Mg 2.1 mg/dL (1.6-2.2), ALP 164 (32-117 U/L), Phos 3.1 mg/dL (3.7-6.5), BUN 21 mg/dL (5-18), Cr 0.51 mg/dL(0.38-0.96), PTH 12 pg/mL (15-65), urine Ca:Cr ratio 0.56 (<0.60), 25-vitD 43 ng/mL (31-80) and 1,25-vitD 5.3 pg/mL (15-60), with abnormal values bolded. An EKG showed normal sinus rhythm and normal QTc. Renal US showed bilateral medullary nephrocalcinosis. She was given IV fluids (NS D5) at 1.5x maintenance, switched to a low-calcium diet (CalciloTM) and daily vit-D supplementation was discontinued. Despite IV hydration for 36 hours, she remained hypercalcemic (Ca 15.6 mg/dL; iCa 1.96 mmol/L) and thus received two doses of IV furosemide to aid diuresis. She was weaned off IV fluids after calcium was <13mg/dL, and iCa 1.29 mmol/L. A genetic micro-array was sent and showed the deletion of chr7.q11.23, consistent with WBS. She was discharged on a low calcium diet and calcium levels have ranged between 10.0-10.8 mg/dL. Her appetite improved, and her weight increased to the 20th%ile without any other dietary changes, by her 15 month visit. Conclusion: Hypercalcemia in WBS can be severe, with the noted calcium level being the highest reported in the literature. The etiology of hypercalcemia in WBS remains unknown and can typically be managed with a low calcium diet and minimizing vitamin D intake. In severe hypercalcemia, IV hydration is the mainstay for acute management, with furosemide, bisphosphonates and other methods reserved for resistant hypercalcemia.