X-linked dominant hypophosphatemic rickets

X-linked Dominant Hypophosphatemic Rickets

X-linked dominant hypophosphatemic rickets (XLH) is a rare genetic disorder characterized by low levels of phosphate in the blood due to impaired renal phosphate reabsorption. This condition leads to rickets, a disease that affects bone development in children, and osteomalacia in adults. XLH is caused by mutations in the PHEX gene, which is located on the X chromosome.

Pathophysiology

XLH is primarily caused by mutations in the PHEX gene, which encodes an endopeptidase involved in bone and dentin mineralization. The PHEX gene mutation leads to increased levels of fibroblast growth factor 23 (FGF23), a hormone that reduces renal phosphate reabsorption and decreases the production of 1,25-dihydroxyvitamin D. The result is hypophosphatemia, or low phosphate levels in the blood, which impairs bone mineralization and leads to the clinical manifestations of rickets.

Clinical Features

Patients with XLH typically present with:

• Short stature
• Bone pain
• Skeletal deformities, such as bowed legs or knock knees
• Dental abnormalities, including spontaneous dental abscesses
• Muscle weakness

Diagnosis

The diagnosis of XLH is based on clinical features, biochemical tests, and genetic testing. Key laboratory findings include:

• Low serum phosphate levels
• Normal or low serum calcium levels
• Elevated alkaline phosphatase levels
• Elevated FGF23 levels

Genetic testing can confirm the diagnosis by identifying mutations in the PHEX gene.

Treatment

The treatment of XLH focuses on correcting phosphate levels and improving bone mineralization. This typically involves:

• Oral phosphate supplements
• Active vitamin D analogs, such as calcitriol or alfacalcidol

Regular monitoring of growth, bone development, and biochemical markers is essential to adjust treatment and prevent complications.

Prognosis

With appropriate treatment, individuals with XLH can lead relatively normal lives, although some may experience persistent bone pain and require orthopedic interventions. Early diagnosis and treatment are crucial to prevent severe skeletal deformities and improve quality of life.

Genetic Counseling

XLH is inherited in an X-linked dominant pattern. This means that the condition can be passed from an affected parent to their children, with a 50% chance of inheritance. Genetic counseling is recommended for affected families to understand the risks and implications of the disorder.

Also see

• Rickets
• Osteomalacia
• Fibroblast growth factor 23
• PHEX gene
• Hypophosphatemia