SP017X-LINKED HYPOPHOSPHATEMIA (XLH) IN ADULTS: CLINICAL AND LABORATORY FINDINGS

Abstract

INTRODUCTION: XLH is a rare inherited disease, with significant morbidity, that is caused by an alteration of the PHEX gene, that results in an increase in serum levels of fibroblast growth factor 23 (FGF-23) and with it, renal phosphate wasting, reduced 1,25- dihydroxyvitamin D and, thus, hypophosphatemia which result in defects in bone mineralization. Affected adults present: short stature, bowed or bent legs, osteomalacia, bone and joint pain, fractures, hearing impairment, extraosseous calcifications, toth abscess, among others. Despite conventional therapy (oral phosphorus supplementation and calcitriol), a significant percentage of patients develop deformities that impact their functionality and quality of life. The aim of this study was to deepen the understanding of the clinical course and the impact on morbidity and serum and urine laboratory findings in adult patients affected by XLH. METHOD(S): Longitudinal study with retrospective data collection of a series of no family-related patients affected by XLH who were followed-up in the Outpatient Services of the Department of Nephrology of the Hospital Universitari i Politecnic La Fe. Demographic, clinical and diagnostic variables were collected from the initial diagnosis in childhood until January 2018. RESULT(S): We collected information about 24 patients, 35,7% of them male, who were diagnosed of XLH at the average age of 3,75+/-3,12 years old and who were followed-up by an average time of 17,92+/-12,09 years. There were statistically significant differences between calciuria and alkaline phosphatase, but we did not find differences on phosphorus, calcium, tubular phosphate reabsorption, parathormone, 1,25-dihydroxycalciferol, creatinine, albumin-to-creatinine ratio or 24 hour proteinuria. Patiets presented: short stature (93%), legs deformity (86%), secondary hyperparathyroidism (SPTH) (29%), nephrocalcinosis (14%), history of fractures (7%), tooth problems (7%) and chronic kidney disease (4%). Every patient had received, during the follow-up, treatment with oral phosphorus and calcitriol. 36,7% of them were also on treatment with analgesics. And 57% of them had underwent corrective surgery. CONCLUSION(S): Most adults affected by XLH present short stature and lower limb deformity despite the classical substitution treatment taken since the childhood and, in many cases, surgical treatment is needed although the significant reduction of the levels of alkaline phosphatase. Treatment is known to be related with relevant and frequent adverse events like SPTH and nephrocalcinosis and is related to poor compliance because of bad gastrointestinal tolerance. It is necessary to advance in better treatments that block the mechanism of the disease to allow a normal childhood growth to these patients, avoiding the consequences of XLH in adulthood, since the current treatment is insufficient and leads to undesirable consequences.