Blau Syndrome: An Unusual Cause of Hypercalcemia in a Child

Objective: To report a case of symptomatic vitamin D-mediated hypercalcemia in a girl with Blau syndrome, a rare granulomatous inflammatory disease occurring in early childhood. Methods: Clinical, laboratory, imaging, and genetic findings are presented along with response to therapy. Results: A 5-year-old girl with a history of surgically treated Graves disease presented with a serum calcium of 13.5 mg/dL (reference range is 9.6 to 10.6 mg/dL), phosphorus of 5.3 mg/dL (reference range is 3.7 to 5.4 mg/dL), parathyroid hormone of 6 pg/mL (reference range is 15 to 65 pg/mL), and an inappropriate 1,25-dihydroxyvitamin D₃ of 64 pg/mL (reference range is 24 to 86 pg/mL). Her hypercalcemia was accompanied by painless, boggy joint effusions and hypertension. Additional testing revealed an elevated angiotensin-converting enzyme concentration and negative fungal and tuberculosis tests. Genetic testing revealed a mutation in the NOD2 gene, confirming the diagnosis of Blau syndrome. Hypercalcemia resolved with treatment of Blau syndrome. Conclusion: Endogenous vitamin D-mediated hypercalcemia is uncommon in children and can be resolved with treatment of the underlying granulomatous disorder. Blau syndrome should be considered in children with vitamin D-mediated hypercalcemia who present with inflammatory joint, skin, and/or eye diseases.