Mild Idiopathic Infantile Hypercalcemia - Part 2: A Longitudinal Observational Study.

CONTEXT: Idiopathic Infantile Hypercalcemia (IIH) is an uncommon disorder with variable clinical features. The natural history and response to dietary calcium and vitamin D restriction in IIH remains unclear.

OBJECTIVE: The aim of this study is to describe the clinical and biochemical response to dietary calcium and vitamin D restriction in a genetically characterized cohort of mild IIH.

METHODS: This is a longitudinal, observational cohort study of 20 children with mild IIH monitored for a median of 21months. Biochemical measures, dietary assessment and yearly renal ultrasound results, since the time of diagnosis, were obtained and assessed prospectively every 4-6 months.

RESULTS: Median age at initial diagnosis was 4·5 months. Median levels of serum calcium (2·82 mmol/l) and 1,25 (OH)2 D (192 pmol/l) were elevated whereas serum PTH was reduced (10 ng/l). Urinary calcium:creatinine ratio was elevated for some, but not all individuals (median 1·49 mmol/mmol). All patients who were managed with a low calcium diet showed an improvement in serum and urinary calcium measures, but the serum concentration of 1,25(OH)2D and 1,25(OH)2D/PTH ratio remained elevated. In 2 of the 11 subjects, renal calcification worsened. There were no differences in response between individuals with CYP24A1 or SLC34A1/A3 variants.

CONCLUSION: The clinical presentation of mild IIH is variable and dietary calcium and vitamin D restriction does not consistently normalize elevated 1,25(OH)2D concentrations or prevent worsening of renal calcification in all cases. Therapeutic options should target the defect in vitamin D metabolism.