X-Linked Hypophosphatemic Rickets
X-linked hypophosphatemic rickets is the most common inherited etiology for rickets with a prevalence of 1 in 20,000 persons.
It is also known as familial hypophosphatemic rickets and X-linked hypophosphatemia.
X-linked hypophosphatemic rickets belongs to a group of disorders in which normal dietary intake of vitamin D is insufficient to achieve normal mineralization of bone. This group is described as Vitamin D resistant rickets.
In X-linked Hypophosphatemia, the female to male ratio is approximately 2:1, and there is no male to male transmission.
Approximately one-third of the cases are sporadic. The defect is in a gene called PHEX, located at Xp22.1. This gene product indirectly regulates the transport of renal phosphates.
The defect at the kidney is isolated renal phosphate wasting, leading to hypophosphatemia.
Craniotabes and rachitic rosary are not seen.
The first usual finding is frontal bossing which may appear as early as 6 months of age.
As the child starts walking, progressive limb deformities become evident leading to disproportionate short stature with short limbs.
Lower limbs are more affected leading to coxa vara, genu valgum, and genu varum. There will be general anterior and lateral bowing of the entire femur along with generalized tibia vara.
Dental abnormalities are common and may often be the presenting complaints. These abnormalities include abscessed noncarious teeth, enamel defects, enlarged pulp chambers, and taurodontium.
Serum calcium – Normal
Serum phosphate – Severely decreased
Serum alkaline phosphatase – Elevated
Parathyroid hormone assay – Normal or slightly elevated
25(OH) vitamin D – Normal
1,25(OH)2 vitamin D – Low or inappropriately normal
Medical treatment – Medical treatment of hypophosphatemic rickets is best managed by a pediatric nephrologist with expertise in metabolic bone disease.
The usual treatment consists of the oral replacement of phosphorus in large doses and the administration of vitamin D (Active form of vitamin D3, Calcitriol).
In April 2018, burosumab (Crysvita), a monoclonal immunoglobulin G1 (IgG1) antibody that binds excess fibroblast growth factor 23 (FGF23), became the first drug approved by the US Food and Drug Administration (FDA) for XLH. Clinical trials showed that the drug normalized phosphorus levels, improved bone mineralization, improved rickets in children, and helped to heal fractures in adults
Orthopedic treatment – Orthotic management has not been efficacious.
If patients are experiencing increasing pain or difficulty walking, surgical correction of angular deformities should be performed.
It is important to work closely with the nephrologist or endocrinologist who is managing medical therapy.
The deformity most commonly seen in patients with hypophosphatemic rickets is a gradual anterolateral bowing of the femur combined with tibia vara.
Multilevel osteotomy is generally required to satisfactorily correct the mechanical axis of the limb. The mechanical axis should be mildly overcorrected at the surgery.
Nephrocalcinosis is a significant complication of medical treatment.
The recurrent deformity is a common sequel of osteotomies.
Adults with hypophosphatemic rickets are prone to the development of arthritis.