Introduction
Rickets is a disease that affects children during developmental stages. Improper development and maturity of cartilage-forming cells cause this condition, resulting in weak bones and deformities. The most common cause of rickets is vitamin D deficiency. However, other rare genetic conditions also cause similar symptoms. Hypophosphatemic rickets is the most frequently diagnosed among the genetic forms of rickets. Hypophosphatemic rickets is caused by low levels of phosphorus in the blood (hypophosphatemia). This can lead to a phosphorus deficiency in the bones, weakening the bones, causing deformities, and stunted growth. Different genetic variants of hypophosphatemic rickets are X-linked hypophosphatemic rickets (1 in 20,000 births), autosomal dominant, and autosomal recessive hypophosphatemic rickets.
What is Autosomal Dominant Hypophosphatemic Rickets?
Autosomal Dominant Hypophosphatemic Rickets (ADHR) is an extremely rare genetic disorder. It usually has a specific type of kidney-related phosphate loss, low levels of phosphate in the blood, and normal levels of calcitriol (1,25-dihydroxy vitamin D3). Low phosphorus levels in the blood lead to rickets, characterized by weak bones, growth problems, and skeletal deformities.
What Causes Autosomal Dominant Hypophosphatemic Rickets?
The disease originates from activating mutations in the FGF23 gene on chromosome 12p13, which codes for fibroblast growth factor 23. These mutations make FGF23 resistant to breakdown, leading to higher hormone levels in the bloodstream. As a result, the body's ability to reabsorb phosphorus in the kidneys and absorb phosphorus and calcium in the intestines decreases, causing abnormal mineralization in the bones.
What Are the Other Genetic Forms of Hypophosphatemic Rickets?
The different genetic forms of hypophosphatemic rickets include:
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X-Linked Hypophosphatemic Rickets (XLH): X-linked dominant and recessive patterns are present. A mutation in the PHEX gene causes it.
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Autosomal Dominant Hypophosphatemic Rickets (ADHR): The autosomal dominant inheritance pattern for hereditary hypophosphatemic rickets only requires one altered gene in each cell to cause the disorder.
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Autosomal Recessive Hypophosphatemic Rickets (ARHR): ARHR is an autosomal recessive condition, meaning both gene copies in each cell have mutations. While the parents of an individual with ARHR carry a mutated gene, they usually do not show symptoms.
Among hypophosphatemic rickets, X-linked hypophosphatemic rickets (XLH) is the most common form, and the other genetic forms are rare. However, hereditary hypophosphatemic rickets can be passed down in an X-linked recessive pattern, also known as Dent disease. This occurs when a mutation in the gene located on the X chromosome is present in males, causing the condition with just one altered copy in each cell. For females to develop the disorder, both gene copies must have mutations, making it less common for them to be affected.
What Are the Symptoms of Autosomal Dominant Hypophosphatemic Rickets?
The symptoms of autosomal dominant hypophosphatemic rickets (ADHR) include:
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Skeletal Deformities: This condition causes bowed legs, deformities of the spine and pelvis, and a characteristic deformity of the wrist called "rickety rosary."
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Delayed Growth and Short Stature: This slows the growth and results in shorter height than normal.
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Bones Become Weaker: Low levels of phosphorus in the blood can lead to weak bones that are more prone to fractures.
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Dental Problems: People may experience tooth problems, such as premature loss of baby teeth, delayed eruption of permanent teeth, or cavities.
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Weakness in the Muscles: Rickets can cause muscle weakness, leading to difficulties with movement and mobility.
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Fatigue can be a symptom, as low phosphorus levels can affect the body's ability to produce energy.
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Bone Pain: Weak bones and skeletal deformities can cause pain and discomfort.
Symptoms can vary in severity and may not appear until later in childhood or adulthood.
How Can Autosomal Dominant Hypophosphatemic Rickets Be Diagnosed?
Autosomal dominant hypophosphatemic rickets can be diagnosed with the help of the following methods.
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Medical History: A healthcare professional will inquire about the family history of a similar condition to help determine autosomal dominant hypophosphatemic rickets.
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Physical Examination: A physical exam is performed to assess the patient's height, weight, and overall appearance, as well as to look for signs of skeletal deformities and muscle weakness.
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Laboratory Tests:
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Blood tests will be performed to measure levels of phosphorus, calcium, alkaline phosphatase, and other factors that can indicate the presence of ADHR.
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Urine tests to detect urinary phosphate and creatinine levels.
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Imaging Tests: X-rays and other imaging tests, such as CT (computed tomography) scans or MRI (magnetic resonance imaging), may assess the bone's condition and detect skeletal deformities.
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Genetic Testing: In some cases, a genetic test is done to confirm the presence of a specific gene mutation responsible for causing ADHR.
How Are Autosomal Dominant Hypophosphatemic Rickets Treated?
The goal of treatment for autosomal dominant hypophosphatemic rickets is to boost growth, alleviate bone or joint pain, fortify bones, and prevent skeletal abnormalities. The treatment for autosomal dominant hypophosphatemic rickets includes:
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Vitamin D Supplementation: Vitamin D is essential to absorb calcium and phosphorus, so supplementation may be necessary to maintain proper levels in the body.
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Phosphate Supplementation: Phosphate supplementation is the cornerstone of treatment for ADHR, as it helps to raise levels of phosphorus in the blood.
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Calcium Supplementation: Calcium supplementation may also be necessary to maintain proper calcium levels in the blood and support bone health.
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Bisphosphonates: Bisphosphonates are a medication that can reduce bone loss and improve bone density in individuals with ADHR.
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Physical Therapy: Physical therapy can benefit individuals with ADHR, as it can help improve muscle strength and prevent joint stiffness.
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Surgery: Surgery may be necessary to correct severe skeletal deformities or to alleviate pain or discomfort in some cases.
Conclusion
Autosomal dominant hypophosphatemic rickets is a rare disorder that causes skeletal deformities, muscle weakness, and symptoms like fatigue and bone pain. The specific treatment plan varies depending on the severity of the condition and the individual's particular symptoms and medical history. Early diagnosis and treatment of this condition can prevent further complications and improve the prognosis. However, dietary changes may also be necessary to improve the treatment outcome. Therefore, it is important to receive ongoing care from a healthcare professional to monitor and adjust the treatment plan.
