Phenotypic characterization of X-linked hypophosphatemia in pediatric Spanish population.

Abstract

BACKGROUND 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. 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. RESULTS The 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. CONCLUSIONS This 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.

Novel PHEX gene locus‐specific database: Comprehensive characterization of vast number of variants associated with X‐linked hypophosphatemia (XLH)

“…Other studies were unable to establish a genotype‐phenotype correlation when comparing patients with truncating variants to those with missense variants (Cho et al, 2005; Rafaelsen et al, 2016; Reid et al, 1989; Zhang et al, 2019). There are also multiple studies describing broad and clinically significant variations in XLH phenotype among patients with the same genotype, including among members of the same family (Holm et al, 2001; Rafaelsen et al, 2016; Rodríguez‐Rubio et al, 2021).…”

Genetic analysis combined with 3D‐printing assistant surgery in diagnosis and treatment for an X‐linked hypophosphatemia patient

“…In the present study, the phenotype of lower limbs in the proband was not milder than her father. 17 Patients with XLH can be observed with knee deformities.…”

Health-related quality of life of X-linked hypophosphatemia in Spain

“…Low levels of phosphate and calcitriol are related to many pathologic changes of XLH [4]. Symptoms are numerous and variable, with different levels of severity [7], and the onset is usually during the first or second year of life [8,9]. Disease manifestations in children include impaired growth [10] with short stature [7] and bone deformities [8,9], especially in lower limbs [7], and radiological signs of active rickets [8,9].…”

“…Symptoms are numerous and variable, with different levels of severity [7], and the onset is usually during the first or second year of life [8,9]. Disease manifestations in children include impaired growth [10] with short stature [7] and bone deformities [8,9], especially in lower limbs [7], and radiological signs of active rickets [8,9]. Moreover, pain [11], poor mineralization of teeth [11] and craniosynostosis [12] have also been described.…”

“…Hospital La Fe, Valencia, Spain 7. Hospital La Paz, Madrid, Spain 8. Hospital Virgen de la Macarena, Seville, Spain 9.…”