Abstract
BackgroundX-linked hypophosphatemia (XLH) is a hereditary rare disease caused by loss-of-function mutations in PHEX gene leading tohypophosphatemia and high renal loss of phosphate. Rickets and growth retardation are the major manifestations of XLH in children, but there is a broad phenotypic variability. Few publications have reported large series of patients. Current data on the clinical spectrum of the disease, the correlation with the underlying gene mutations, and the long-term outcome of patients on conventional treatment are needed, particularly because of the recent availability of new specific medications to treat XLH.ResultsThe RenalTube database was used to retrospectively analyze 48 Spanish patients (15 men) from 39 different families, ranging from 3 months to 8 years and 2 months of age at the time of diagnosis (median age of 2.0 years), and with XLH confirmed by genetic analysis. Bone deformities, radiological signs of active rickets and growth retardation were the most common findings at diagnosis. Mean (± SEM) height was − 1.89 ± 0.19 SDS and 55% (22/40) of patients had height SDS below—2. All cases had hypophosphatemia, serum phosphate being − 2.81 ± 0.11 SDS. Clinical manifestations and severity of the disease were similar in both genders. No genotype—phenotype correlation was found. Conventional treatment did not attenuate growth retardation after a median follow up of 7.42 years (IQR = 11.26; n = 26 patients) and failed to normalize serum concentrations of phosphate. Eleven patients had mild hyperparathyroidism and 8 patients nephrocalcinosis.ConclusionsThis study shows that growth retardation and rickets were the most prevalent clinical manifestations at diagnosis in a large series of Spanish pediatric patients with XLH confirmed by mutations in the PHEX gene. Traditional treatment with phosphate and vitamin D supplements did not improve height or corrected hypophosphatemia and was associated with a risk of hyperparathyroidism and nephrocalcinosis. The severity of the disease was similar in males and females.
Highlights
X-linked hypophosphatemia (XLH) is a hereditary rare disease caused by loss-of-function mutations in PHEX gene leading tohypophosphatemia and high renal loss of phosphate
The disease is caused by a defective function of PHEX gene [1, 9,10,11,12,13], leading to elevated circulating concentrations of fibroblast growth factor 23 (FGF23) [14], relatively low levels of 1,25 dihydroxyvitamin d [1,25(OH)2D], hyperphosphaturia secondary to decreased proximal tubular reabsorption of phosphate and hypophosphatemia [8, 10, 15]
This study is justified at least by the following reasons: (1) XLH is a rare disease and few publications provide data on large series of patients; (2) XLH has a broad phenotypic variability and additional information is required to better characterize the clinical spectrum of the disease and to explain why the number of cases diagnosed usually does not correspond to the estimated prevalence of the disease; (3) It is important to share data of patients with genetically confirmed XLH in order to facilitate the finding of a potential phenotype—genotype correlation and to have current data that can be compared for the assessment of the new therapies
Summary
X-linked hypophosphatemia (XLH) is a hereditary rare disease caused by loss-of-function mutations in PHEX gene leading tohypophosphatemia and high renal loss of phosphate. This study is justified at least by the following reasons: (1) XLH is a rare disease and few publications provide data on large series of patients; (2) XLH has a broad phenotypic variability and additional information is required to better characterize the clinical spectrum of the disease and to explain why the number of cases diagnosed usually does not correspond to the estimated prevalence of the disease; (3) It is important to share data of patients with genetically confirmed XLH in order to facilitate the finding of a potential phenotype—genotype correlation and to have current data that can be compared for the assessment of the new therapies
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
