Introduction
Primary hyperoxaluria type 1 (PH1) is a rare and severe genetic disorder that affects the kidneys primarily. The word "primary" signifies that the disease is present at birth, "hyper" means higher than normal, and "oxaluria" refers to the presence of oxalate in the urine.
Out of the three types of hyperoxaluria, that is, PH1, PH2, and PH3, PH1 is the most widespread, caused by mutations in the AGXT gene, leading to excessive production of oxalate in the body. Normally, the kidneys filter and excrete oxalate, but in PH1, it accumulates in the kidneys and urinary tract, forming calcium oxalate stones. Excessive calcium oxalate can harm other parts of the body as well.
Prompt diagnosis and treatment are imperative for maintaining kidney function and overall health. If left untreated, PH1 can progress to kidney failure, requiring a transplant or dialysis to survive. Adhering to the treatment plan prescribed by the healthcare team, which may include current medications and clinical trials, can enhance the outcomes.
What Are the Indications of PH1?
The signs of PH1 can vary from mild to severe and emerge at any stage from infancy to early adulthood. They are unique to each individual and can include renal stones, blood in the urine, and urinary tract infections. For those with early-onset PH1, known as infantile oxalosis, the symptoms can be severe and occur before six months. On the other hand, those with milder forms of PH1 may not show symptoms for more than 40 to 50 years.
The typical age at which symptoms appear is around five to six years old. Infants suffering from PH1 may also show symptoms of failure to thrive, which means they do not grow and develop normally and may appear weak. If left untreated, primary hyperoxaluria type 1 (PH1) can lead to severe consequences, including kidney failure. As the condition progresses, individuals may experience the following symptoms:
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Decreased urine production.
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Absence of urine, exhaustion.
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General feelings of illness.
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Lack of appetite.
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Nausea and vomiting.
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Pale skin and swelling in the hands or feet.
How Is PH1 Identified?
Diagnosing a genetic or rare disease can be challenging. In order to make a diagnosis, healthcare practitioners investigate a patient's medical history, family history, and symptoms, and perform a physical examination and blood and urine tests.
However, the diagnosis of PH1 is confirmed by genetic testing for mutations in the AGXT gene. If the genetic test does not uncover any mutations, a liver biopsy may be performed, which involves obtaining a small piece of the liver using a needle. The liver cells contain the enzyme that helps prevent oxalate buildup, and if there is not enough of this enzyme present or it is absent, this can assist in making the diagnosis.
What Are the Treatment Options for PH1?
The treatment of PH1 aims to reduce the accumulation of calcium oxalate and maintain kidney function. The following steps may help prevent calcium oxalate kidney stones, but it is recommended to consult with a healthcare professional:
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Consuming a lot of fluids, primarily water.
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Taking oral potassium citrate to prevent the formation of calcium oxalate crystals.
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Using drugs such as Thiazides to reduce calcium in the urine.
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Avoiding high doses of vitamin C or D as they may contribute to kidney stones.
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Consuming plenty of calcium through diet and drinks.
Treatment with vitamin B6 (pyridoxine) may be prescribed to decrease oxalate production in the body. Although not everyone with PH1 will respond to pyridoxine, a three-month trial is typically recommended after diagnosis. In some cases, dialysis may be used to remove oxalate, but it is often unable to keep pace with the body's oxalate production.
Organ transplantation is another treatment option, but the best approach has yet to be determined. Options include simultaneous liver and kidney transplants, a liver transplant followed by a kidney transplant, a kidney transplant, or a liver transplant only. Lumasiran, produced by Alnylam Pharmaceuticals, has been approved by the FDA to treat PH1 and reduce oxalate levels in children and adults.
What Are Some Tips for Managing Primary Hyperoxaluria Type 1 (PH1)?
Dealing with a condition such as primary hyperoxaluria type 1 (PH1) can be a difficult experience for the individual affected and their loved ones, both physically and emotionally. Feelings of sadness, fear, frustration, and anger are common when living with PH1, and it is normal for emotions to change over time. Awareness of any illness or disease impacting one's mental health is important.
A chronic condition such as PH1 can cause stress, which is why managing it is crucial for maintaining both physical and emotional well-being. Although stress is a part of life, excessive stress can negatively impact one's health. It is important to remember that emotions and physical health are interconnected. Maintaining a healthy emotional state can improve overall health and help in living longer. Set achievable goals, be flexible, and allow room for mistakes. Maintaining a positive outlook, engaging in activities that a person enjoys, and spending time with those who bring joy to life can all contribute to staying healthy.
What Is the Prognosis of Primary Hyperoxaluria Type 1?
The outcome for individuals with PH1 is uncertain and depends on the diagnosis and treatment timing. If left untreated, PH1 will result in the progressive failure of the kidneys and, ultimately, death. In most cases, end-stage kidney disease is reached between the third and fifth decades. However, 80 percent of patients diagnosed with PH1 in infancy will experience end-stage kidney disease by the age of three. Half of those diagnosed with the disease during childhood will develop end-stage kidney disease by age 15, and death in the first decade of life is a possibility for those with early-onset disease. Post-organ transplant, some people with PH1 have lived normal or nearly normal lifespans.
Conclusion
In conclusion, primary hyperoxaluria type 1 (PH1) is a rare and severe genetic disorder that affects the kidneys and can lead to kidney failure if left untreated. The condition is caused by mutations in the AGXT gene and results in excessive oxalate production in the body, leading to the formation of calcium oxalate stones. Early detection and treatment are critical for preserving kidney function and health. Symptoms of PH1 can range from mild to severe and can include frequent kidney stones, blood in the urine, and urinary tract infections. The diagnosis is confirmed through genetic testing for mutations in the AGXT gene, and treatment options include medications, vitamin B6, dialysis, and organ transplantation.
