Vitamin D resistant rickets is a rare bone disorder characterized by the kidneys’ impaired ability to reabsorb phosphate, leading to chronically low phosphate levels in the blood. This deficiency results in soft and weak bones, which can bend easily. It is distinct from common rickets caused by insufficient dietary vitamin D intake or lack of sun exposure. The condition’s primary characteristic is its poor response to typical vitamin D supplementation, which is why it earned the “resistant” designation.
Distinguishing Features and Symptoms
Vitamin D resistant rickets often becomes apparent in infancy or early childhood, around the time a child begins to walk. The persistent low phosphate levels, a condition known as hypophosphatemia, hinder the proper mineralization of bone and cartilage. This impaired mineralization leads to a range of physical symptoms.
Children with this condition frequently develop bowed legs, medically termed genu varum, or knock knees, known as genu valgum. They may also experience short stature and general bone pain due to the weakened skeletal structure. Other common signs include a waddling gait and joint stiffness, reflecting the impact on bone and joint health. Dental abnormalities are also common, such as dental abscesses and delayed tooth eruption, which stem from issues with dentin mineralization.
Genetic Causes
The “resistant” aspect of this condition stems primarily from its inherited nature, rather than a simple dietary deficiency. X-linked hypophosphatemia (XLH) is the most common genetic form of vitamin D resistant rickets, accounting for over 80% of cases. XLH is caused by a mutation in the PHEX gene, located on the X chromosome. This gene normally helps regulate phosphate levels in the body.
A mutation in the PHEX gene leads to an excessive amount of fibroblast growth factor 23 (FGF23), a hormone that regulates phosphate and vitamin D metabolism. Elevated FGF23 levels cause the kidneys to excrete too much phosphate into the urine, preventing its reabsorption back into the bloodstream. This excess FGF23 also interferes with the kidney’s ability to activate vitamin D.
Diagnosis and Treatment Approaches
Diagnosing vitamin D resistant rickets involves a thorough clinical assessment combined with specific laboratory and imaging tests. Healthcare providers evaluate a child’s symptoms and growth patterns, looking for the characteristic skeletal deformities. Blood tests are a cornerstone of diagnosis, revealing low phosphate levels, while calcium levels are normal or slightly low. Elevated alkaline phosphatase, an enzyme indicating increased bone turnover, is also observed, alongside elevated FGF23 levels and normal 25-hydroxyvitamin D levels.
Urine tests further support the diagnosis by showing an inappropriately high excretion of phosphate, confirming the kidney’s impaired reabsorption. X-rays of bones reveal typical rickets-related abnormalities such as cupping, fraying, and widening of the growth plates. Genetic testing, especially for mutations in the PHEX gene, provides a definitive confirmation of X-linked hypophosphatemia.
Treatment strategies for vitamin D resistant rickets focus on correcting phosphate balance and promoting bone mineralization. The primary therapeutic approach involves lifelong oral phosphate supplements, given multiple times a day to maintain more stable blood levels. These are combined with active vitamin D analogs, such as calcitriol, which bypass the need for kidney activation that is impaired in this condition.
Newer targeted therapies have also emerged, offering more specific interventions. Burosumab, a monoclonal antibody, directly targets and blocks the activity of FGF23. By inhibiting FGF23, burosumab helps the kidneys reabsorb more phosphate and increases the active form of vitamin D, directly addressing the root cause of phosphate wasting. Careful and ongoing monitoring of blood and urine parameters is necessary during treatment to ensure optimal phosphate levels are maintained and to minimize potential complications such as kidney stones or hypercalcemia.