Idiopathic Infantile Hypercalcaemia-Genetic, Biochemical and Clinical Outcomes in a Small Cohort

Idiopathic Infantile Hypercalcaemia (IIH) is rare; thus data on investigation, treatment and outcome are limited. Monogenic causes have been implicated in some cases.

To report on the biochemical profile and response to treatment of infants with IIH and yield of testing for variants in genes involved in calcium sensing and vitamin D metabolism (CASR, AP2S1, GNA11, CYP24A1).

Retrospective analysis of the clinical records and biochemistry of 14 infants with IIH, diagnosed between March 2011 and March 2014, with genetic testing in nine infants.

Median [range] age at presentation was 17 days [5-53]. Median calcium concentration was 2.92 mmol/L [2.79-4.03]. PTH was suppressed or inappropriately normal (median 0.85pmol/L; [0.3-3.1]) with high or normal urinary calcium:creatinine (median 3.3 mmol/mmol; [0.4-7.9]). 25OHD was normal or low (median 48 nmol/L; [17-218]). Serum calcium dropped in all treated with low calcium formula with subsequent elevated PTH (median 8.2 pmol/L) in 9/14 associated with low 25OHD (median 33 nmol/L) despite serum calcium concentration in the upper part of the reference interval (median 2.67 mmol/L). No pathogenic genetic variants were identified but 7/9 patients had common non-pathogenic variants, and in 5 there was more than 1.

IIH occurred at a younger age than typically reported. Biochemical findings were suggestive of variations in calcium sensing and/or vitamin D metabolism; however, only common, non-pathogenic genetic variants were identified. Prolonged use of low calcium feeds should be monitored closely with PTH measurements due to the potentially deleterious effect on bone health.