A clinician's guide to X-linked hypophosphatemia

Abstract

X-linked hypophosphatemia (XLH) is the prototypic disorder of renal phosphate wasting, and the most common form of heritable rickets. Physicians, patients, and XLH support groups have all expressed concerns about the dearth of information about this disease and the lack of treatment guidelines which frequently lead to missed diagnoses or mismanagement. This perspective addresses the recommendation by conferees for the dissemination of concise and accessible treatment guidelines for clinicians arising from the “Advances in Rare Bone Diseases Scientific Conference,” held at the National Institutes of Health in October 2008. We briefly review the clinical and pathophysiologic features of the disorder, and offer this guide in response to the conference recommendation, base on our collective accumulated experience in the management of this complex disorder.

Impaired quality of life in adults with X-linked hypophosphatemia and skeletal symptoms

“…However, the effect of treatment in adults on skeletal complications (osteoarthritis, enthesopathies) is still unknown (2,35).…”

“…Therapy with phosphate salts and vitamin D analogs aim at reducing bone pain, improving dentition, correcting leg deformities, improving adult height and decreasing the number of surgeries (2,3). Initiation at early ages is recommended as the early initiation of treatment optimises final body height results (2,3).…”

“…Most adults are treated with phosphate supplements and vitamin D analogs to reduce extent of osteomalacia and to improve fractures healing or surgery recovery; however, there is no consensus on the indications and duration of treatment in adults. Serum alkaline phosphatase activity is measured to quantify the extent of osteomalacia; some biological tests (25 OH vitamin D, calcaemia, phosphatemia, calciuria, phosphaturia, parathyroid hormone serum level) are performed for the monitoring of XLH, in order to avoid some complications such as hypercalciuria or hyperparathyroidism (2,3).…”

“…On the other hand, other long-term skeletal complications (osteoarthritis and enthesopathies) are also responsible for musculoskeletal pain and fatigue likely leading to disability and altered quality of life (QoL) (2). Visual analogic pain scales may help to quantify the degree of pain and disability but are not appropriate to assess the disease burden.…”

Serum Fibroblast Growth Factor 23 Is a Useful Marker to Distinguish Vitamin D-Deficient Rickets from Hypophosphatemic Rickets

“…X-linked hypophosphatemic rickets (HR) is the most common form of heritable rickets and is manifested by fibroblast growth factor 23 (FGF23) excess and renal phosphate wasting [15,16]. Clinical and radiographic features are mostly similar to vitamin D-deficient rickets (DR).…”