primary hyperoxaluria type 2

Primary hyperoxaluria type 2 (PH2) is a rare inherited disorder that affects the body's ability to metabolize glyoxylate, leading to an excessive buildup of oxalate in the kidneys and other organs. This condition is characterized by:

• Recurrent kidney stones: PH2 leads to the formation of calcium oxalate stones in the kidneys, which can cause severe pain and discomfort.
• Nephrocalcinosis: The deposition of calcium oxalate crystals in the renal parenchyma (kidney tissue) can lead to scarring and damage to the kidneys.
• End-stage kidney disease (ESKD): PH2 can progress to ESKD, a life-threatening condition where the kidneys are no longer able to filter waste products from the blood effectively.

PH2 is caused by mutations in the GRHPR gene, which codes for an enzyme that helps prevent oxalate buildup in the body. This genetic defect leads to an accumulation of glyoxylate and its conversion to oxalate, resulting in the symptoms associated with PH2 [2][3][5][8].

In terms of prevalence, PH2 is a rare condition, affecting less than 1 in 1 million people worldwide [9]. It is inherited in an autosomal recessive pattern, meaning that individuals must inherit two copies of the mutated gene (one from each parent) to develop the condition.

Overall, primary hyperoxaluria type 2 is a serious and potentially life-threatening condition that requires prompt medical attention.

Primary hyperoxaluria type 2 (PH2) is a rare genetic disorder characterized by the overproduction of oxalate, leading to the formation of calcium oxalate stones in the kidneys. The signs and symptoms of PH2 can vary depending on the severity of the disease, but here are some common ones:

• Recurring kidney stones: One of the most common symptoms of PH2 is the formation of recurring kidney stones, which can cause severe pain and discomfort (1).
• Kidney damage: The excess oxalate in the body can lead to kidney damage, including nephrocalcinosis (deposition of calcium oxalate in the renal parenchyma) and end-stage kidney disease (ESKD) (11).
• Urinary tract infections: People with PH2 are more prone to urinary tract infections due to the presence of stones in the urinary tract (7).
• Blood in the urine: In some cases, people with PH2 may experience blood in their urine due to the damage caused by the stones (7).
• Failure to thrive: Infants and young children with PH2 may experience failure to thrive due to the disease's impact on kidney function (3).

It's essential to note that the symptoms of PH2 can vary depending on the severity of the disease, and some people may not exhibit any symptoms at all. If you suspect that you or a loved one has PH2, it's crucial to consult with a healthcare professional for proper diagnosis and treatment.

References: (1) [1] (7) [7] (11) [11]

Diagnostic Tests for Primary Hyperoxaluria Type 2

Primary hyperoxaluria type 2 (PH2) is a rare genetic disorder characterized by the overproduction of oxalate, leading to kidney and bladder stones. Accurate diagnosis is crucial for effective management and treatment. Here are the diagnostic tests used to diagnose PH2:

• Urinary Metabolite Screening: This test detects increased levels of oxalate in urine, which is a hallmark of PH2 [4][5]. The test involves collecting a 24-hour urine sample to measure oxalate concentration.
• Genetic Testing: Molecular genetic testing can identify biallelic pathogenic variants in the GRHPR gene, confirming the diagnosis of PH2 [1].
• Kidney Biopsy: A kidney biopsy may be performed to assess the extent of kidney damage and to rule out other conditions that may cause similar symptoms.
• Imaging Studies: Imaging studies such as ultrasound, CT scans, or MRI may be used to evaluate the extent of kidney involvement and to detect any complications.

Additional Tests

Other tests may be performed to confirm the diagnosis and rule out other conditions. These include:

• Plasma Oxalate Levels: Measuring plasma oxalate levels can help differentiate PH2 from other forms of hyperoxaluria.
• Glycolate and Glycerate Analysis: Analyzing urine for glycolate and glycerate can also aid in diagnosis.

Diagnostic Teams

A multidisciplinary diagnostic team may be involved in diagnosing PH2, including:

• Genetics
• Nephrology

These teams work together to provide a comprehensive evaluation and diagnosis of the condition.

References: [1] Dec 2, 2008 — The diagnosis of PH2 is established in a proband by identification of biallelic pathogenic variants in GRHPR by molecular genetic testing. [4] A diagnostic workup in an individual with hyperoxaluria demonstrates increased concentration of oxalate in urinary metabolite screening. [5] The Invitae Primary Hyperoxaluria panel analyzes 3 genes associated with primary hyperoxaluria, a disorder of glyoxylate metabolism associated with renal damage.

Treatment Options for Primary Hyperoxaluria Type 2

Primary hyperoxaluria type 2 (PH2) is a rare genetic disorder characterized by the overproduction of oxalate, leading to recurrent kidney stones and potentially life-threatening complications. While there are no definitive cures for PH2, various treatment options can help manage symptoms and slow disease progression.

Dietary Modifications

1. Oxalate restriction: Patients with PH2 should follow a strict diet that limits or avoids foods high in oxalates, such as spinach, beets, rhubarb, and chocolate [4].
2. Calcium supplementation: Calcium citrate or calcium carbonate can help bind dietary oxalates, reducing their absorption and excretion [4].

Pharmacological Interventions

1. Vibegron (VB6): This medication has been shown to be effective in reducing urinary oxalate levels and slowing disease progression in patients with PH2 [7].
2. Nedosiran: An investigational RNA interference agent designed to inhibit the expression of hepatic lactate dehydrogenase, which is thought to contribute to hyperoxaluria [8].

Other Therapeutic Approaches

1. Dialysis: In severe cases, dialysis may be necessary to remove excess oxalates from the blood and prevent further kidney damage.
2. Kidney transplantation: A kidney transplant can provide a cure for PH2 by replacing the diseased kidneys with healthy ones [11].
3. Liver transplantation: In some cases, a liver transplant may also be necessary to address underlying metabolic issues contributing to hyperoxaluria.

Emerging Therapies

1. RNA interference (RNAi) therapy: This innovative approach has shown promise in treating PH2 by targeting the genetic defect responsible for the disease [15].
2. CRISPR/Cas9-mediated glycolate oxidase disruption: A novel therapeutic strategy that has been effective in treating primary hyperoxaluria type 1, which may also be applicable to PH2 [13].

It is essential to note that each patient's response to treatment may vary, and a comprehensive treatment plan should be tailored to individual needs. Consultation with a healthcare professional specializing in rare diseases or nephrology is crucial for effective management of primary hyperoxaluria type 2.

The differential diagnosis for primary hyperoxaluria type 2 (PH2) includes several conditions that can present with similar symptoms.

• Hypercalciuria: This condition is characterized by an excessive amount of calcium in the urine, which can lead to kidney stones and other complications.
• Hypocitraturia: This condition involves a low level of citrate in the urine, which can increase the risk of developing kidney stones.
• Cystinuria: This is a rare genetic disorder that affects the kidneys' ability to reabsorb certain amino acids, leading to an excessive amount of these substances in the urine.

These conditions can be distinguished from PH2 through molecular genetic testing, which can identify biallelic pathogenic variants in the GRHPR gene.