Background: Hereditary hypophosphatemic rickets (HR) is a group of rare diseases with disordered phosphate metabolism. The Norwegian cohort of HR patients has not previously been described.
Objective and hypotheses: The aim of the study was to characterize the genotype, phenotype, and complications to treatment in a national cohort of Norwegian children HR.
Method: For assessment of genotype, Sanger sequencing of PHEX, FGF23, DMP1, ENPP1, and KL were performed. Multiplex ligand-dependent probe amplification (MLPA) analysis was performed to detect larger duplications or deletions in PHEX. In one family, exome sequencing was performed to identify the genotype. For assessment of phenotype and complications to treatment, the medical records were reviewed.
Results: The prevalence of HR was one in 45 000 children. We identified 26 patients (17 females, nine males) from 17 families. There were 21 familiar and five sporadic cases. PHEX mutations were found in 21 subjects (81%). Two brothers had mutations in FAM20C. In three sporadic cases, no pathogenic mutation was identified. 11 of 18 X-linked HR (XLHR) patients had elevated levels of intact parathyroid hormone (iPTH) at the time of diagnosis, and all 18 patients developed hyperparathyroidism during follow-up. In patients with XLHR, the maximum level of iPTH was higher for patients with missense mutations than patients with other mutations. Nephrocalcinosis was observed in nine XLHR individuals, and was related to higher treatment doses of calcitriol and phosphate. The height Z-score at follow-up correlated negatively with age at start of medical treatment, but was not related to treatment doses of phosphate and calcitriol.
Conclusion: A genetic diagnosis is important, as new anti-FGF23 treatment may become available in the future. Early diagnosis and medical treatment are probably more important than phosphate dosing to optimize growth and minimize the occurrence of complications.
20 - 22 Sep 2014
European Society for Paediatric Endocrinology