Background: Both CYP24A1 and SLC34A1 gene mutations are responsible for idiopathic infantile hypercalcemia (IIH). Whereas loss-of-function mutations in CYP24A1 (25-OH-vitamin D-24-hydroxylase) lead to a defect in the inactivation of active 1,25(OH)2-vitamin D3, mutations in SLC34A1 encoding renal sodium-phosphate co-transporter NaPi-IIa lead to primary renal phosphate wasting combined with an inappropriate activation of vitamin D. The presence of mutations in both genes has not been reported in the same patient until today.
Aim: Our aim is to show the clinical findings of the siblings as well as the parents who carry mutations in both genes.
Case Report: Case 1: Hypercalcemia was detected in a 13-moths-old boy with urinary tract infection (UTI). Hydration and furosemide were given for hypercalcemia. Oral phosphor solution was started since serum phosphor and TRP was lower. All therapy was stopped when calcium and phosphor were within normal.
Case 2: Hypercalcemia was detected in a 6-month-old girl with (UTI) (Table 1). High dose vitamin-D had been not given. Serum calcium normalized with hydration and furosemide (10.5 mg /dL).
Bilaterally medullary nephrocalcinosis was detected in both siblings. Serum Ca and P were within normal limits at follow-up in both siblings. Siblings and their parents all carry a homozygous stop codon mutation (p.R466* ) in CYP24A1. Interestingly both siblings and the father also have a heterozygous splice-site mutation (IVS6(+1)G>A) in SLC34A1. Father has nephrocalcinosis at right kidney. Siblings' paternal aunt and paternal uncle also have nephrocalcinosis and, their paternal grandmother and grandfather was second cousin.
Conclusion: A bi-allelic loss-of-function mutation in the CYP24A1 gene was identified as responsible for hypercalcemia, hypercalciuria and nephrocalcinosis. In addition, a heterozygous mutation in the SLC34A1 gene although not being the main pathogenic factor, might contribute to the severe phenotype of both patients.
|At the admission||Case 1||Case 2||Father||Mother|
|Weight,kg (SD)||10.5 (-0.01)||7.5 (0.11)|
|PTH, pg/mL (12-88)||<6||4.6||12||22.7|
|25OHD3, ng/mL (10-70)||6.9||18.91||11.2||16.4|
|1,25OHD3, pg/mL (19.6-65)||19.9||47.56||12.74||26.06|
|Spot Urine Ca/Cr||1.69||1.7||0.22||0.05|
19 - 21 Sep 2019
European Society for Paediatric Endocrinology