Left Ventricular Hypertrophy in Patients with X-Linked Hypophosphataemia.

Abstract

X-linked hypophosphatemia (XLH) is a rare genetic disorder with x-linked dominant inheritance. The mutation on the PHEX gene increases fibroblast growth factor 23 (FGF23), causing loss of phosphorus at the proximal tubule. Most pediatric patients debut in the first two years with short stature and bow legs. Conventional treatment consists of oral supplements with phosphorus and calcitriol. Since 2018, burosumab is approved as a novel therapeutic option for XLH with promising results. The purpose of this study is to share our experience with two cases of XLH treated with burosumab. These patients presented with a broad phenotypical difference - the one with the most severe radiological phenotype developed left ventricular hypertrophy 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 patients biochemistry and quality of life. The left ventricular hypertrophy was stabilized 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 yet unclear. The most studied populations are patients with XLH or chronic kidney disease, as both associate high levels of FGF23. To date, cardiovascular involvement in XLH has been described in patients treated with conventional treatment, so it would be interesting to investigate if the early start of burosumab at the time of diagnosis of XLH prevents the occurrence of cardiovascular manifestations.