X-linked hypophosphatemic rickets

X-linked Hypophosphatemic Rickets
Other names	XLH, X-linked hypophosphatemia
Specialty	Endocrinology, Pediatrics
Symptoms	Bone pain, skeletal deformities, growth retardation
Complications	Dental abnormalities, hearing loss, enthesopathy
Usual onset	Early childhood
Duration	Lifelong
Causes	Genetic mutation (PHEX gene)
Risk factors	Family history of XLH
Diagnostic method	Blood tests (low phosphate), genetic testing
Differential diagnosis	Other forms of rickets, osteomalacia
Treatment	Phosphate supplements, vitamin D analogs
Medication	Calcitriol, phosphate salts
Prognosis	Variable, depends on treatment and complications
Frequency	Rare

X-linked hypophosphatemic rickets (XLH) is a genetic disorder characterized by low levels of phosphate in the blood, leading to bone softening and weakening. This condition is primarily caused by mutations in the PHEX gene, which is located on the X chromosome. As a result, XLH is typically inherited in an X-linked dominant pattern, affecting both males and females, though females may have milder symptoms due to X-chromosome inactivation.

Symptoms and Signs

The primary symptoms of XLH include bone pain, skeletal deformities such as bowed legs or knock knees, and growth retardation. These symptoms usually begin in early childhood. Other potential complications include dental abnormalities, progressive hearing loss, and enthesopathy (calcification of tendons and ligaments).

Causes

XLH is caused by mutations in the PHEX gene, which leads to an excess of fibroblast growth factor 23 (FGF23). This excess inhibits phosphate reabsorption in the kidneys, resulting in hypophosphatemia (low blood phosphate levels) and consequently, rickets in children and osteomalacia (softening of the bones) in adults.

Diagnosis

Diagnosis of XLH is based on clinical evaluation, family history, and laboratory tests showing persistently low levels of phosphate. Genetic testing can confirm a mutation in the PHEX gene. Differential diagnosis should exclude other causes of rickets and hypophosphatemia, such as dietary deficiencies or other genetic disorders.

Treatment

Treatment of XLH aims to correct phosphate levels and manage symptoms. This typically involves supplementation with phosphate salts and vitamin D analogs such as calcitriol. Regular monitoring and adjustments of therapy are necessary to avoid complications such as nephrocalcinosis (calcium accumulation in the kidneys).

Prognosis

The prognosis for individuals with XLH varies. With early and ongoing treatment, many of the complications of XLH can be managed, allowing individuals to lead active lives. However, some may experience persistent issues related to bone and tooth health, hearing, and physical growth.

Epidemiology

XLH is a rare disease, affecting approximately 1 in 20,000 individuals worldwide. It is the most common form of hereditary rickets.

See Also

• Rickets
• Phosphate metabolism
• Genetic disorders

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