MIM 307 800]

(X-linked hypophosphatemic rickets)

Prevalence: about 1/20,000. The most common cause of hypophosphatemia. X-linked dominant transmission with variable expression of a mutation of the PHEX gene (Xp22.1). This gene is expressed in osteocytes and odontoblasts, and codes for an endopeptidase regulating the synthesis of FGF-23 (Fibroblast Growth Factor 23). These loss-of-function mutations lead to increased FGF-23 synthesis, decreased renal phosphate reabsorption, and insufficient bone mineralization.

Clinical manifestations:

• signs of rickets: short stature, deformity of the lower limbs (genu varum or vagum), waddling gait, bone pain, stress fractures (Looser's zones), muscle weakness. X-rays: signs of rickets and osteomalacia (enlargement of the metaphyses of the long bones)
• early fusion of the cranial sutures: craniosynostosis the diagnosis of which is later than in isolated or syndromic craniosynostoses not related to hypophosphatemia; headache, signs of intracranial hypertension, sometimes Chiari malformation type I or syringomyelia
• abnormalities of the tooth dentin or enamel, caries

Diagnosis: hypophosphatemia with hyperphosphaturia, high blood levels of FGF-23, normal blood levels of Ca and parathyroid hormone.

Treatment: vitamin D and phosphate supplements. Clinical trials with burosumab, a recombinant antibody directed against FGF-23.

Orthopaedic treatments: osteotomies or epiphysiodesis with a high risk of post-operative recurrence.

Anesthetic implications: 

fragile bones, preoperative eye fundus examination especially in the presence of signs of intracranial hypertension

References : 

-         Hamdy NAT, Harvengt P, Usardi A.
X-linked hypophosphatemia : the medical expert’s challenges and the patient’s concerrns on their journey with the disease.
Arch Pédiatr 2021 ; 28 :612-8

-        Di Rocco F, Rothenbuhler A, Adamsbaum C, Bacchetta J, Pejin Z et al.
Orthopedic and neurosurgical care of X-linked hypophosphatemia.
Arch Pédiatr 2021 ; 28 :599-605

Updated: November 2021