Home            Past Issues            About IP            About IAP           Author Information            Subscription            Advertisement              Search  

   
Correspondence

Indian Pediatr 2015;52: 163-164

Pamidronate for Long-term Control of Hypercalcemia Associated With Williams Syndrome


Javed Ismail

Department of Pediatrics, AIIMS, Ansari Nagar, New Delhi, India.
Email: [email protected]

     


Hypercalcemia in Williams Syndrome is usually mild and transient, but in about 5% of patients, it may be severe, and associated with medullary nephro-calcinosis [1].

A 3-year-old boy, second born of non-consanguineous parents with uneventful perinatal history, presented to us with global developmental delay and failure to thrive. He had history of feeding difficulty, constipation, increased frequency of micturition, and increased irritability, and failure to thrive. Examination revealed facial features characteristic of Williams syndrome. Initial blood investigations revealed total serum calcium of 14.5 mg/dL and phosphorus of 6.2 mg/dL. Serum 25-OH vitamin D was 21.4 ng/mL, serum i-PTH was 2.5 pg/mL and urinary calcium creatinine (Ca/Cr) ratio was 2.4. Repeat values were consistent with PTH-independent hypercalcemia and hypercalciuria. Ultrasonography of kidneys showed bilateral dense medullary nephrocalcinosis. Genetic analysis using Fluorescence in situ hybridization (FISH) was done which confirmed deletion in region of 7q11.23.

We started the child on calcium-restricted diet, intravenous fluids for hydration, and furosemide to reduce serum calcium levels. Despite these measures, there was no decrease in serum calcium levels for 48 hours and the repeat serum calcium level was 15.2mg/dL. We administered single dose of pamidronate (1mg/kg) as intravenous infusion over 6 hours. Gradually the serum calcium levels decreased over a period of 3 days to 10.2 mg/dL. On subsequent follow up visits, at 2,4, 8, 12 weeks, and 6 and 12 months, the serum calcium level and urinary calcium creatinine ratio were in normal range. His irritability, feeding difficulty and constipation resolved, and he was gaining weight.

Though the association of Williams syndrom with hypercalcemia is well established, the exact mechanism causing the same is still unravelled. Various mechanisms like increased Vitamin D sensitivity [2] and defective calcitonin synthesis and release [3] have been proposed. Recently, TRPC 3 channel was found to be overexpressed in intestine and kidneys of these patients, implying that over-absorption from these tissues as the cause of hypercalcemia [4]. Pamidronate acts by inhibiting osteoclast activity, thus reducing bone absorption and turnover. In our patient, similar to a previous report [5], hypercalcemia was well controlled with pamidronate therapy, speculating that increased bone metabolism might be the likely cause. Though pamidronate has not been approved for use in children, phase III trials are underway for its use in children with osteogenesis imperfecta.

References

1. Committee on Genetics. American Academy of Pediatrics: Health care supervision for children with Williams syndrome. Pediatrics. 2001;107:1192-204.

2. Forfar JO, Balf CL, Maxwell GM, Tompsett SL. Idiopathic hypercalcaemia of infancy; Clinical and metabolic studies with special reference to the aetiological role of vitamin D. Lancet. 1956;270:981-8.

3. Culler FL, Jones KL, Deftos LJ. Imparied calcitonin secretion in patients with Williams syndrome. J Pediatr. 1985;107:720-3.

4. Letavernier E, Rodenas A, Guerrot D, Haymann JP. Williams-Beuren syndrome hypercalcemia: Is TRPC3 a novel mediator in calcium homeostasis? Pediatrics. 2012;129:e1626-30.

5. Sangun O, Dundar BN, Erdogan E. Severe hypercalcemia associated with Williams syndrome successfully treated with pamidronate infusion therapy. J Pediatr Endocrinol Metab. 2011;24:69-70.

 

Copyright © 1999-2014 Indian Pediatrics