Left Ventricular Hypertrophy in Patients with X-Linked Hypophosphataemia

Abstract

X-linked hypophosphatemia (XLH) is a rare genetic disorder with X-linked dominant inheritance. Mutations in the PHEX gene increase fibroblast growth factor 23 (FGF23) concentrations, causing loss of phosphorus at the proximal tubule. Most pediatric patients debut in the first two years with short stature and bowed legs. Conventional treatment consists of oral supplements with phosphorus and calcitriol. Since 2018, burosumab has been approved as a novel therapeutic option for XLH, with promising results. The purpose of this study was to share our experience with two cases of XLH treated with burosumab. These patients presented with a broad phenotypical differences. One had the most severe radiological phenotype and developed left ventricular hypertrophy (LVH) and left ventricular dysfunction with preserved ejection fraction. Treatment with burosumab was well-tolerated and was followed by radiological stability and a striking improvement in both blood biochemistry and quality of life. The LVH was stable and left ventricular function normalized in the patient with cardiac involvement. In recent years many studies have been carried out to explain the role of FGF23 in cardiovascular damage, but the exact pathophysiological mechanisms are as yet unclear. The most intensively studied populations are patients with XLH or chronic kidney disease, as both are associated with high levels of FGF23. To date, cardiovascular involvement in XLH has been described in patients treated with conventional treatment, so it would be of interest to investigate if early use of burosumab at the time of diagnosis of XLH would prevent the occurrence of cardiovascular manifestations.

Fibroblast growth factor 23 and calcium‐phosphate metabolism in relation to cardiovascular risk factors in patients with type 1 diabetes

“…There are no data of treatment of patients with other diseases with heart function abnormalities related to high FGF23 levels. 42 Previous studies have demonstrated that FGF23 levels are higher in obese individuals versus normal weight individuals and that BMI is positively correlated with FGF23 even in different study populations. 20,28,40,[43][44][45] In our study we found these results only in our control group.…”

“…There are no data of treatment of patients with other diseases with heart function abnormalities related to high FGF23 levels. 42 …”

“…In a patient with XLH and left ventricular dysfunction, the left ventricular function normalized during burosumab treatment. There are no data of treatment of patients with other diseases with heart function abnormalities related to high FGF23 levels 42 …”

FGFR4 and Klotho Polymorphisms Are Not Associated with Cardiovascular Outcomes in Chronic Kidney Disease

“…Beyond these merely observational studies, in a randomized trial of 120 CKD G3 patients, administration of the phosphate-binding drug sevelamer reduced FGF-23 levels significantly but had no impact on cardiac hypertrophy or function [40]. Furthermore, Takashi et al [41] did not observe the development of LVH in 24 adult patients with hypophosphatemic rickets, who are lifelong exposed to elevated plasma FGF-23, albeit these data were recently challenged [42].…”

Cardiovascular health in pediatric patients with X-linked hypophosphatemia under two years of burosumab therapy

“…Pediatric patients with XLH have increased prevalence of obesity ( 5 ) and evidence of unfavorable body composition ( 6 ), potentially placing them at risk for metabolic complications ( 7 ). Left ventricular hypertrophy (LVH) with several potential contributing factors has been reported in children affected by debilitating XLH ( 8 ). The chronic exposure to elevated levels of FGF23 have been proposed as a risk factor for cardiac morbidity, based upon its having been linked with cardiac hypertrophy in the context of chronic renal failure ( 9 ).…”