Introduction
X-linked hypophosphatemic rickets is a genetic disorder in which the level of phosphate is below the normal range in the blood. Phosphate is a form of phosphoric acid widely found in bones and teeth. Along with calcium, it is considered one of the essential minerals in the body. Many food sources are rich in phosphates, such as eggs, nuts, dairy products, corn, rice, and lentils. Phosphate helps in the formation and growth of tissues, DNA (deoxyribonucleic acid), and RNA (ribonucleic acid). In addition, phosphate balances the other minerals and vitamins, such as vitamin D, iodine, and zinc. Hypophosphatemia is a term used to describe the low levels of phosphate in the blood. Hypophosphatemia can affect anyone and is a common condition. When the level of phosphate declines in the body, it may affect essential functions such as muscle contraction, building and repairing bones and teeth, and essential nervous system functions.
What Is X-Linked Hypophosphatemic Rickets?
The term rickets is added in X-linked hypophosphatemic because the affected children also develop rickets. It is a rare genetic disorder in which the level of phosphate in the blood is very low. It affects around one in 20,000 newborns. Rickets is a condition that leads to the weakening of the bones due to vitamin D deficiency or inherited disorders. The X-linked hypophosphatemic rickets affects average growth and development in children. Many of the deformities are easily noticeable and may become severe if neglected for a long time.
What Causes X-Linked Hypophosphatemic Rickets?
It is caused due to an alteration in genetic coding for PHEX (phosphate regulating endopeptidase homolog X-linked), a protein that regulates the growth factor 23 (FG23). The PHEX gene is needed to store the phosphate for normal functioning in the body. However, the impaired PHEX gene adheres to the kidneys to reabsorb phosphate into the bloodstream. This leads to too much excretion of phosphate through the kidneys and, thus very low phosphate level.
This condition is termed “X-linked” meaning the defective gene is carried on the X chromosome. It mainly affects males, as males have X and Y chromosomes. The risk of developing this condition is low in females because they carry two X chromosomes, so the one defective chromosome generally does not respond. But these females are carriers, meaning there are chances of passing the condition to offspring. Males generally pass the defective gene to their daughters.
What Are the Clinical Features of X-Linked Hypophosphatemic Rickets?
The symptoms of X-linked hypophosphatemic rickets are visible from an early age (around age one or two). Some of the symptoms include the following:
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Reduced daily activities.
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Impaired growth.
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Bone tenderness.
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Increased tendency of fractures.
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Muscle spasm.
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Leg bowing (a condition in which both legs curve outwards at the knees).
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Periapical abscess.
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Widening of the wrist.
How Are X-Linked Hypophosphatemic Rickets Diagnosed?
Depending on the signs and symptoms, some of the diagnostic factors are taken into consideration.
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Clinical Examination - A doctor does a complete physical examination to know the severity of the condition. Along with this, family medical history is also noted.
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X-Ray - It is one of the beneficial testing methods to diagnose rickets. The radiographic features of the lower limbs and hands show abnormal growth plates. A scoring method is used in X-rays of rickets to denote the severity. It is generally termed a rickets severity score (RSS). The 10 in the score denotes extreme severity or degree of rickets.
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Blood Test - A blood test generally helps in diagnosing the low level of phosphate and the high level of alkaline phosphate. The blood sample is usually taken from the arm’s vein. A fine needle is inserted in the vein, and the desired amount of sample is collected in a vial or a test tube. There might be slight discomfort, but it is a simple procedure completed within ten minutes. The blood sample is then sent to a laboratory for further evaluation. Along with the blood test to check the phosphate levels, a genetic blood test is also done, especially for newborns, as it helps in early diagnosis and treatment.
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Urine Test - It checks if the kidneys are properly reabsorbing the phosphate. A healthcare expert will give a sterile container in which the urine sample should be collected.
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Kidney Ultrasound - To evaluate the manifestation of the diagnosis and kidney stones, a common symptom in this condition, a doctor may advise this test. It is an imaging test that uses high magnetic waves to get proper images of the kidney. The test takes around half an hour to complete.
How Are X-Linked Hypophosphatemic Rickets Managed?
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The FDA (food and drug administration) has approved Burosumab-TWZA for treating kids under one year and adults.
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Conventional treatment includes a dose of oral phosphate salts such as calcitriol.
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Proper brushing, flossing, maintaining oral hygiene, and regular dental visits help prevent dental abscesses.
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Strict monitoring is beneficial during the treatment as it will help see the treatment's efficiency.
What Is the Prognosis of X-Linked Hypophosphatemic (XLH) Rickets?
The long-term prognosis of XLH (X-linked hypophosphatemia) patients is largely dependent on their phosphate and vitamin D therapy. Untreated XLH can result in bone deformities and growth restriction. Oral phosphate and vitamin D therapy, on the other hand, can increase their height. Even if development has improved with therapy, it is frequently impossible to reach a standard adult height. It is occasionally possible for leg abnormalities to be corrected naturally without the need for surgery, but this is not usually the case. When leg abnormalities worsen and interfere with a child's ability to walk normally, it is vital to contact an orthopedic surgeon to assess the surgical alternatives.
Kidney stones, high blood pressure, oral infections, and electrolyte imbalances are other secondary problems of XLH that may develop despite treatment. Children who have XLH must thus be closely monitored by a nephrologist who can help families with the right monitoring and treatment of this illness.
Conclusion
X-linked hypophosphatemic rickets is a rare genetic disorder in which the level of phosphate in the blood is below the normal range, and it is interlinked with rickets which causes deformity and weakening of bones. This condition is mainly seen in males, and the symptoms are easily visible from age one. This condition does not cause any severe complications only if diagnosed and treated on time. Some complications include kidney stones, high blood pressure, and dental infections. Also, if left untreated, it may lead to bony abnormalities and limited growth. Most cases show improvement by taking the prescribed medications for a specific time.
