Focus
Rachitismo ipofosforemico X-linked
X-linked hypophosphatemia
Laura Lucchetti 1, Danilo Fintini2, Marco Cappa2, Francesco Emma1
1UOC di Nefrologia e Dialisi, Dipartimento Pediatrie Specialistiche,
2UOC di Endocrinologia, Dipartimento Universitario-Ospedaliero,
Ospedale Pediatrico Bambino Gesω IRCCS, Roma
Settembre 2020 - pagg. 430 -436 | DOI: 10.53126/MEB39430
Abstract
X-linked hypophosphatemia (XLH) is an X-linked disorder with dominant penetration,
caused by mutations in the PHEX gene, which encodes for an endopeptidase that is predominantly
expressed in osteoblasts, osteocytes and odontoblasts. PHEX mutations
cause increased production of fibroblast growth factor 23 (FGF23) that in turn leads to
hypophosphatemia by causing inhibition of the renal phosphate reabsorption and of the
synthesis of active 1,25-dihydroxyvitamin D. In children XLH is characterised by rickets,
bone pain, physical dysfunction, impaired growth, disproportionate short stature, lowerlimb
deformities, pathological fractures, dental malposition and dental abscesses. Although
phenotype may be variable in severity, early diagnosis and treatment are critical
to improve outcome. Laboratory tests show hypophosphatemia associated with hyperphosphaturia
and elevated alkaline phosphatase, while parathormone and calcium levels
are normal. For decades, patients have been treated with conventional therapy, including
active vitamin D supplementation and fractionated daily doses of oral phosphate
salts. However, these therapies rarely normalise the phenotype. More recently,
burosumab, a recombinant human IgG1 monoclonal antibody against FGF-23, has
been introduced for the treatment of XLH. In phase 2 trials, burosumab has been shown
to improve significantly clinical symptoms, as well as biological and radiological signs
of rickets.
Parole chiave
Suggerite dall'AI
IT
Burosumab
Classificazione MeSH
Alkaline Phosphatase (19)
Antibodies, Monoclonal, Humanized (12)
Bone Diseases, Metabolic (12)
Burosumab (3)
Familial Hypophosphatemia (3)
Fibroblast Growth Factor-23 (4)
Genes, X-Linked (14)
Hypophosphatemia (5)
Nephrocalcinosis (12)
PHEX Phosphate Regulating Neutral Endopeptidase (2)
Rickets, Hypophosphatemic (8)
Vitamin D (60)
Contenuto riservato
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Corrispondenza: laura.lucchetti@opbg.net