Primary Hyperoxaluria Type 1
Description
Primary Hyperoxaluria Type 1 (PH1) is a rare genetic disorder that affects the kidneys‘ ability to process oxalate, a naturally occurring compound found in many foods. This buildup of oxalate leads to the formation of calcium oxalate crystals, which can damage the kidneys and potentially lead to kidney failure. Understanding PH1 is crucial for early diagnosis, management, and improving the quality of life for affected individuals.
Genes Involved
PH1 is caused by mutations in the AGXT gene, which is responsible for producing the enzyme alanine:glyoxylate aminotransferase (AGT). This enzyme is crucial for the breakdown of glyoxylate, a precursor to oxalate. When the AGXT gene is mutated, AGT activity is reduced, leading to an accumulation of glyoxylate and subsequently increased oxalate production.
Recognizing the Signs and Symptoms
PH1 can manifest with various symptoms, ranging from mild to severe. Some common signs include:
- Kidney stones: Frequent kidney stones, particularly in childhood, are a hallmark symptom of PH1.
- Painful urination: Stones passing through the urinary tract can cause pain during urination.
- Blood in urine (hematuria): Blood in the urine may indicate kidney damage or irritation.
- Fatigue: Persistent fatigue can be a sign of kidney dysfunction.
- Nausea and vomiting: These symptoms can arise due to kidney failure or the buildup of toxins in the body.
- Bone pain: Some individuals with PH1 may experience bone pain due to the excessive excretion of calcium in urine.
- Growth delay: In children, PH1 can hinder growth due to impaired kidney function.
Causes
Primary Hyperoxaluria Type 1 is an inherited genetic disorder. Individuals inherit two copies of the AGXT gene, one from each parent. A mutation in one or both copies of the AGXT gene can lead to PH1. The severity of the disorder can vary depending on the specific mutations inherited.
Inheritance/recurrence risk
PH1 is inherited in an autosomal recessive pattern. This means that an individual must inherit two copies of the mutated AGXT gene, one from each parent, to develop the disorder. If both parents carry the mutated gene, there is a 25% chance that their child will inherit both copies and develop PH1, a 50% chance of inheriting one copy and being a carrier, and a 25% chance of inheriting neither copy and being unaffected.
