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Primary Hyperoxaluria Type 2, Genetic Testing

Primary hyperoxaluria type 2 (PH2) is another rare genetic disorder, similar to primary hyperoxaluria type 1 (PH1), characterized by the overproduction and accumulation of oxalate in the body. However, PH2 is caused by mutations in a different gene compared to PH1. The prevalence of PH2 is lower than that of PH1 and is estimated at around one case per million population.

Primary hyperoxaluria type 2 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).

Critical features of primary hyperoxaluria type 2 include:

  • Genetic Basis: Primary hyperoxaluria type 2 is caused by GRHPR gene mutations, which provide instructions for making the enzyme glyoxylate/hydroxypyruvate reductase (GR/HPR). Mutations in this gene lead to a deficiency of the GR/HPR enzyme, impairing the breakdown of glyoxylate and hydroxypυruvate, precursors to oxalate. As a result, oxalate accumulates in the body.
  • Oxalate Accumulation: Elevated oxalate levels can lead to kidney stones forming and the deposition of calcium oxalate crystals in various organs, similar to PH1.
  • Kidney Stones: Recurrent kidney stones are a common manifestation of PH2, causing symptoms such as abdominal pain, blood in the urine, and urinary tract infections.
  • Kidney Damage: Chronic oxalate deposition in the kidneys can result in progressive damage, ultimately leading to kidney failure.
  • Systemic Effects: Like PH1, Primary hyperoxaluria type 2 can involve the accumulation of oxalate crystals in other organs, leading to systemic complications beyond the kidneys.
  • Symptoms: Symptoms can include those associated with kidney stones, such as abdominal pain and other signs of kidney dysfunction.
  • Diagnosis involves clinical evaluation, imaging studies to detect kidney stones, and laboratory tests to measure urinary oxalate levels. Genetic testing is necessary to identify mutations in the GRHPR gene and confirm the diagnosis of PH2.
  • Treatment: The management of Primary hyperoxaluria type 2 is generally similar to that of PH1, involving strategies to reduce oxalate production, increase the elimination of oxalate through the urine, and prevent the formation of kidney stones. Treatment may include medications, dietary modifications, and, in severe cases, transplantation.

As with primary hyperoxaluria type 1, early diagnosis and intervention are crucial in primary hyperoxaluria type 2 to minimize complications and preserve kidney function. Individuals with a family history of primary hyperoxaluria or those experiencing symptoms associated with the condition should seek medical attention for proper evaluation and diagnosis. Treatment plans are often individualized based on the specific genetic mutation and clinical presentation.

Primary hyperoxaluria type 2 is caused by the presence of homozygous pathogenic variants in the GRHPR gene encoding the enzyme glyoxylate/hydroxypyruvate reductase. This enzyme transforms glyoxylate into glycolate, a substance easily eliminated by the body.

The c.103del (p.Asp35fs) and c.403_404+2del mutations are the most common in patients with primary hyperoxaluria type 2. The c.103del (p.Asp35fs) variant produces a reading frame shift, resulting in a non-functional truncated protein. It is the most frequent variant, occurring in approximately 40% of published cases, and is mainly found in Caucasian individuals of European or North American origin.

The c.403_404+2del variant in exon 4 is a four-base deletion that causes defective splicing of the mRNA and results in a non-functional protein. This variant is predominantly found in Asian patients.

Primary hyperoxaluria type 2 genetic testing analyzes the 7 most frequent pathogenic mutations of the GRHPR 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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