Hereditäre hypophosphatämische Rachitis: Neue Aspekte zur Pathogenese, Diagnostik und Therapie

Hereditary hypophosphatemic rickets (HR) is a genetically and clinically heterogenous group of conditions caused by renal phosphate wasting and characterized by the consequences of the loss of mineralized bone. The clinical features are variable. In childhood, short stature and leg malalignment due to deformity of the lower extremities are the leading clinical symptoms of rickets and osteomalacia. In adulthood, pseudofractures, mobility problems, and arthrosis, as well as extra-skeletal mineral depositions, also occur. The most common form of is X‑linked hypophosphatemic rickets (XLHR) caused by mutations in the PHEX gene, located on the X‑chromosome. PHEX encodes for the “phosphate-regulating gene with homologies to endopeptidase,” which is involved in the regulation of fibroblast growth factor FGF23. An increase in fibroblast growth factor 23 (FGF23) induced by mutations in PHEX or other genes of rare forms of HR lead to forced phosphate reabsorption via the kidneys and thereby to renal phosphate wasting. The rarer forms of HR, which are inherited via either an autosomal-dominant (ADHR) or an autosomal-recessive (ARHR), or even a X‑chromosomal recessive pattern, are nowadays divided on the basis of whether they elicit an increase in FGF23 or induce phosphate wasting independently of FGF23. This is of diagnostic and therapeutic significance. Although treatment for HR has so far been carried out in the form of several daily doses of phosphate and vitamin D metabolites that are possibly still active, an anti-FGF23 antibody, burosumab, has recently become available. Today, burosumab (Crysvita®) has been approved in Europe only for the treatment of children and adolescents with XLHR. With this treatment, normalization of renal phosphate wasting and subsequent improvement of rickets and osteomalacia can be achieved. In the short and middle term, a clear clinical improvement has been observed. Long-term results, including data on application in adult XLH patients, are still lacking.