engleski

INFANTILE HYPERCALCEMIA DUE TO HOMOZYGOUS CYP24A1 MUTATION IN A PATIENT WITH NEUROFIBROMATOSIS TYPE 1: A CASE REPORT

Abstract: Idiopathic infantile hypercalcemia (IIH) is characterized by severe symptomatic hypercalcemia. It is caused by mutations in CYP24A1 and SLC34A1 resulting in increased vitamin D sensitivity and elevated serum 1, 25(OH)2D3 with subsequent hypercalcemia and hypercalciuria. SLC34A1 mutations additionally lead to primary renal phosphate wasting and hypophosphatemia. Contrarly, neurofibromatosis (NF) is associated with vitamin D deficiency, so supplementation of vitamin D is beneficial. Yet, NF is sometimes complicated by hypophosphatemic osteomalacia and hyperparathyroidism. We report a case of a 14 years old male who initially presented at the age of 5 months with profound hypercalcemia, vomiting, dehydration, weight loss, hypotonia, and hypercalciuria. He was exclusively breastfed and received 1000 IU of vitamin D for prophylaxis. Serum 25-OH vitamin D and 1, 25(OH)2D3 levels were normal, while parathyroid hormone level was undetectable. Besides, he had hypophosphatemia and osteomalacia. A low calcium/vitamin D diet was initiated. Ultrasound showed increased echogenicity of the renal pyramids at the age of 3 years and kidney stones at the age of 5. Serum calcium and phosphate levels were normal and hypercalciuria was excluded. Furthermore, he fulfilled clinical criteria for neurofibromatosis type 1 and started prophylaxis with 600 IU vitamin D. Neverthless, after two months of prophylaxis, he developed hypercalciuria with suppressed PTH and hyperphosphaturia, so vitamin D was restricted again. By the age of 7, he suffered from recurrent renal colic. The kidney stones were fragmented with extracorporeal shock wave lithotripsy and excreted in the urine. Since then the patient has been treated with hydrochlorothiazide, which lead to normalization of urine calcium/creatinine ratio and renal ultrasound. Moreover, catch-up in growth and development was observed. Finally, genetic analysis identified homozygous missense variant CYP24A1 c.1186C>T, p. (Arg396Trp). IIH has not yet been described in individuals with NF1. Both conditions adversely affect complex phosphocalcic metabolism. Hydrochlorothiazide is a useful treatment option. Further investigation is required to facilitate appropriate management and treatment of this challenging patients.

idiopathic infantile hypercalcemia ; CYP24A1 mutations ; SLC34A1 mutatuins ; vitamin D ; pediatrics

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