Autosomal dominant hypophosphatemic rickets caused by a novel pathogenic variant in FGF23

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Abstract We report a child with autosomal dominant hypophosphatemic rickets (ADHR) due to a novel pathogenic variant in fibroblast growth factor 23 (FGF23). A 1 year 10 month old girl was referred for rickets that did not respond to a single mega dose of vitamin D (600 000 IU orally). Laboratory work-up revealed: calcium, 9.8 mg/dL (2.5 mmol/L) [reference range (ref.) 8-11 mg/dL (2-2.7 mmol/L)]; phosphorus, 2.1 mg/dL (0.7 mmol/L) [ref. 2.5-4.5 mg/dL (0.8-1.5 mmol/L)]; alkaline phosphatase, 1453 IU/L (24.2 µkat/L) [ref. 142-335 U/L (2.4-5.6 µkat/L)]; 25-hydroxyvitamin D, 20.6 ng/mL (51.4 nmol/L) [ref. 30-100 ng/mL (74.8 −249.6 nmol/L)]; 1,25-dihydroxyvitamin D, 47 pg/mL (117.3 pmol/L) [ref. 31-87 pg/mL (77.4 −217.2 pmol/L)]; parathyroid hormone, 54.2 pg/mL (54.2 ng/L) [ref. 18 −80 pg/mL (18-80 ng/L)]. Tubular reabsorption of phosphate was 61.2%. Whole-exome sequencing identified a novel de novo heterozygous in-frame deletion variant, c.515_529 del (p.(Pro172_Arg176del)) in exon 3 of FGF23 confirming the diagnosis of ADHR and the variant was submitted to ClinVar. She was started on phosphate and calcitriol with clinical and biochemical improvement. She had mild iron deficiency anemia and iron supplementation (2 mg/kg/day) was initiated, allowing further reduction in phosphate supplementation.

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