Adult Presentation of X-Linked Hypophosphatemia

Adult X-linked hypophosphatemia (XLH) patients present with specific symptoms, including enthesopathies (e.g., ossification of the longitudinal ligament (OPLL), osteophytes around the large joint, and enthesopathy in the Achilles tendon), the development of severe secondary and tertiary hyperparathyroidism (SHPT/THPT) and the subsequent progression of chronic kidney disease (CKD). In addition, these patients exhibit the typical phenotypes of osteomalacia, such as pseudofracture and fracture in weight-bearing bones, odontitis, and tooth abscess. The mechanism underlying enthesopathy development is unknown; however, a common underlying mechanism among XLH and autosomal recessive hypophosphatemic rickets, ARHR1.2, due to mutations in PHEX, DMP1, and ENPP1, is assumed. Clarification of the pathogenesis and drug discovery for this complication is an urgent issue to address, as many adult XLH patients suffer subsequent debilitating nervus symptoms or impingement syndrome, and existing treatments are ineffective. Severe SHPT and THPT are associated with conventional therapy, including active vitamin D and phosphate supplementation, and complicated and careful adjustment of the dosage by experienced clinicians is required to avoid SHPT/THPT. Burosumab is a very effective therapy without risk for the development of SHPT/THPT. However, the indication of this drug should be carefully considered along with the cost-effectiveness, guidelines or recommendations and health care system of each country.