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Primary Hyperoxaluria Type 1, Genetic Testing

Primary hyperoxaluria type 1 (PH1) is a rare genetic disorder characterized by the overproduction of oxalate, which usually gets eliminated through the urine. In individuals with PH1, an enzyme deficiency leads to oxalate accumulation in the kidneys and other organs, forming crystals. Over time, these crystals can result in kidney stones, kidney damage, and other complications. The prevalence of PH1 is less than 3 cases per million population, with a higher incidence in North African and Middle Eastern countries.

Primary hyperoxaluria type 1 genetic testing is included in Diagnostiki Athinon Monogenic Diseases Genetic Testing along with approximately 100 other inherited diseases, including cystic fibrosis (71 mutations) and hereditary breast cancer (genes BRCA1 415 mutations & BRCA2 419 mutations).

The key features of Primary Hyperoxaluria Type 1 are:

  • Genetic Basis: PH1 is caused by AGXT gene mutations, which provide instructions for making the alanine-glyoxylate aminotransferase (AGT) enzyme. This enzyme is essential for synthesizing glyoxylate, a precursor to oxalate. Mutations in AGXT lead to a deficiency of AGT, allowing excess glyoxylate to be converted into oxalate, leading to its accumulation.
  • Oxalate Accumulation: Elevated levels of oxalate in the body can lead to the formation of kidney stones and deposits of calcium oxalate crystals in the kidneys and other organs. Over time, these deposits can cause kidney damage and may lead to kidney failure.
  • Kidney Stones: Recurrent kidney stones are a common early symptom of PH1. These stones can cause pain, blood in the urine, and urinary tract infections.
  • Progressive Kidney Damage: Chronic oxalate deposition in the kidneys can lead to progressive damage, ultimately resulting in kidney failure. Kidney failure may necessitate the need for dialysis or kidney transplantation.
  • Systemic Effects: Oxalate crystals can accumulate in other organs, such as the bones, eyes, heart, and blood vessels, leading to a range of systemic complications besides kidney involvement.
  • Symptoms: Symptoms may vary but can include abdominal pain, urinary tract infections, kidney stones, and, in advanced cases, signs of kidney failure.
  • Diagnosis involves clinical evaluation, imaging studies to detect kidney stones, and laboratory tests to measure urinary oxalate levels. Genetic testing can confirm the presence of mutations in the AGXT gene.
  • Treatment: The management of PH1 typically involves a combination of strategies to reduce oxalate production, increase oxalate elimination through the urine, and prevent the formation of kidney stones. These may include medications, dietary modifications, and, in some cases, liver or combined liver-kidney transplantation.

Primary hyperoxaluria type 1 is a severe condition that requires ongoing medical management. Early diagnosis and intervention are crucial for minimizing complications and preserving kidney function. Individuals with a family history of PH1 or those experiencing symptoms associated with the condition should seek medical attention for proper evaluation and diagnosis.

Primary hyperoxaluria type 1 (HP1) is an autosomal recessive disease. It is caused by alterations in the AGXT gene, which codes for the enzyme AGT, or L-alanine-glyoxylate aminotransferase, found in the liver. This enzyme transforms glyoxylate into glycine. When this enzyme does not function properly, glyoxylate is transformed into oxalate, which forms insoluble calcium salts that accumulate in the kidneys and other organs.

The c.508G>A mutation (p.Gly170Arg) accounts for 30% of the alleles detected in PH1 patients. It has been found in both homozygosis and compound heterozygosis. Other common variants in PH1 patients are c.454T>A (p.Phe152Ile) and c.731T>C (p.Ile244Thr).

Primary hyperoxaluria type 1 genetic testing analyzes the 15 most frequent pathogenic mutations of the AGXT gene.

The technique used for genetic testing analyzes only the gene's specific mutations, which are the most important and frequent in the literature. However, it should be noted that there are likely other gene or chromosomal mutations in the gene to be tested that cannot be identified with this method. Different analysis techniques can be used for these cases, such as next-generation sequencing (NGS).

Additional information
Results Time4 - 5 Weeks
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