primary hyperoxaluria type 3

Primary hyperoxaluria type 3 (PH3) is a rare genetic disorder characterized by recurring calcium oxalate stones beginning in childhood or adolescence, and on occasion, nephrocalcinosis or reduced kidney function. This condition most often presents in childhood, with signs or symptoms related to stones including hematuria, frequent urination, dysuria, blood visible in the urine, or stone-associated pain.

Key characteristics of PH3:

• Early onset of recurrent urolithiasis (kidney and bladder stones)
• Good preservation of kidney function in most patients
• Lower urine oxalate levels compared to other types of primary hyperoxaluria
• Higher urine calcium and uric acid levels

PH3 is caused by mutations in the HOGA1 gene, which codes for a mitochondrial enzyme involved in glyoxylate metabolism. This genetic defect leads to an excess of oxalate production, resulting in kidney stones and other complications.

References:

• Wang et al., 2015 [1] - discussed the typical clinical characteristic of PH3 as early onset of recurrent urolithiasis
• Monico et al., 2011 [2] - compared patients with PH3 to those with PHI and PHII, highlighting lower urine oxalate levels in PH3 patients
• Primary hyperoxaluria type 3 (PH3) is characterized by recurring calcium oxalate stones beginning in childhood or adolescence and, on occasion, nephrocalcinosis or reduced kidney function [10]

Primary hyperoxaluria type 3 (PH3) is a rare liver disease that can cause various signs and symptoms, particularly in children and adolescents.

Common Signs and Symptoms:

• Recurring calcium oxalate stones beginning in childhood or adolescence
• Nephrocalcinosis (calcium deposits in the kidneys)
• Reduced kidney function
• Hematuria (blood in the urine)
• Frequent urination
• Dysuria (painful urination)
• Blood visible in the urine

These symptoms can vary depending on the severity of the disease and individual factors. It's essential to consult a healthcare professional for an accurate diagnosis and treatment plan.

Age of Onset: Primary hyperoxaluria type 3 most often presents in childhood, with a median age of 2-3 years. However, symptoms can appear at any age, and it's crucial to investigate further if you or a loved one experiences these signs and symptoms.

Prevalence: Type 1 is the most common form, affecting 8 out of 10 people with hyperoxaluria. Types 2 and 3 each affect 1 in 10 people with hyperoxaluria.

References:

• [4] Symptoms can develop anytime from infancy to adulthood.
• [5] Common symptoms include the formation of stones throughout the urinary tract (urolithiasis) and kidneys (nephrolithiasis).
• [6] Primary hyperoxaluria can be challenging to diagnose. Learn about the warning signs of PH including recurring kidney stones in adults & children, ...
• [10] Primary hyperoxaluria type 3 (PH3) is characterized by recurring calcium oxalate stones beginning in childhood or adolescence and, on occasion, nephrocalcinosis or reduced kidney function.
• [14] Clinical description: Primary hyperoxaluria type 3 (PH3) is characterized by recurring calcium oxalate stones beginning in childhood or adolescence and, on occasion, nephrocalcinosis or reduced kidney function.

Diagnostic Tests for Primary Hyperoxaluria Type 3

Primary hyperoxaluria type 3 (PH3) is a rare genetic disorder characterized by recurring calcium oxalate stones, nephrocalcinosis, or reduced kidney function. Diagnosing PH3 can be challenging, but several diagnostic tests can help confirm the condition.

Urine Tests

• Urine tests are often the first step in diagnosing PH3. These tests measure oxalate and other substances in the urine over a 24-hour period.
• The test involves collecting urine in a special container for 24 hours, which is then sent to a lab for analysis.

Blood Tests

• Blood tests can help check how well the kidneys are working and measure oxalate levels in the blood.
• These tests are essential in diagnosing PH3, as they can help identify any kidney damage or dysfunction.

Targeted Variant Analysis

• Targeted variant analysis is a genetic test that analyzes specific genes associated with primary hyperoxaluria.
• This test can help identify mutations in the HOGA1 gene, which is responsible for PH3.

Sequence Analysis of the Entire Coding Region

• Sequence analysis of the entire coding region involves analyzing the DNA sequence of the HOGA1 gene to identify any mutations or variations.
• This test can help confirm a diagnosis of PH3 and rule out other conditions.

Deletion/Duplication Analysis

• Deletion/duplication analysis is a genetic test that analyzes the HOGA1 gene for deletions or duplications.
• This test can help identify any genetic abnormalities associated with PH3.

Microsatellite Instability Testing (MSI)

• Microsatellite instability testing (MSI) is a genetic test that analyzes microsatellites in the DNA sequence of the HOGA1 gene.
• This test can help identify any genetic mutations or variations associated with PH3.

According to [10], Primary hyperoxaluria type 3 (PH3) is characterized by recurring calcium oxalate stones beginning in childhood or adolescence and, on occasion, nephrocalcinosis or reduced kidney function. PH3 most often presents in childhood (median age 2 to 3 years) with signs or symptoms related to stones including hematuria, frequent urination, dysuria, blood visible in the urine, or stone-associated pain.

References: [1], [10]

Treatment Options for Primary Hyperoxaluria Type 3 (PH3)

Primary hyperoxaluria type 3 (PH3) is a rare genetic disorder characterized by recurring calcium oxalate stones, nephrocalcinosis, or reduced kidney function. While there are no specific treatments that can cure PH3, various medical therapies and pharmacotherapies can help manage the condition.

• Medical Therapy: Treatment of pyridoxine-resistant primary hyperoxaluria frequently involves combinations of all available therapies. This may include medications such as vitamin B6 (pyridoxine) to reduce oxalate production in the liver.
• Pharmacotherapy: The goal of pharmacotherapy is to reduce urine supersaturation of calcium oxalate, thereby preventing stone formation and kidney damage. Medications like siRNA drug lumasiran have been investigated for their potential in treating PH3.
• Dialysis: In some cases, dialysis may be necessary to help remove excess oxalate from the body. However, this is not a long-term solution and does not address the underlying cause of the condition.
• Kidney-Liver Transplantation: In severe cases, kidney-liver transplantation may be considered as a treatment option for PH3.

Emerging Therapies

Recent studies have investigated the use of RNAi drugs like nedosiran, which is a once-monthly subcutaneous injection under investigation for all three types of primary hyperoxaluria. This emerging therapy shows promise in reducing oxalate production and preventing kidney damage.

It's essential to note that treatment options may vary depending on individual circumstances and the severity of the condition. Consultation with a healthcare professional is necessary to determine the best course of action for managing PH3.

References:

• [1] Treatment of pyridoxine-resistant primary hyperoxaluria frequently involves combinations of all available therapies and may ultimately entail kidney-liver transplantation.
• [4] Getting treatment for hyperoxaluria can help reduce the chances of long-term kidney damage.
• [9] The RNAi drug nedosiran is a once-monthly subcutaneous injection under investigation for all 3 types of primary hyperoxaluria.
• [10] A kidney transplant or kidney and liver transplant can treat primary hyperoxaluria.

Differential Diagnosis of Primary Hyperoxaluria Type 3

Primary hyperoxaluria type 3 (PH3) is a rare genetic disorder characterized by recurring calcium oxalate stones, nephrocalcinosis, and reduced kidney function. When diagnosing PH3, it's essential to consider differential diagnoses that can mimic its clinical presentation.

Conditions to Consider:

• Hypercalciuria: Excessive calcium in the urine can lead to calcium oxalate stone formation, similar to PH3.
• Hypocitraturia: Low citrate levels in the urine can increase the risk of calcium oxalate stones.
• Cystinuria: A genetic disorder that affects cystine reabsorption, leading to cystine stones and potential kidney damage.

Other Considerations:

• Kidney Stones: Calcium oxalate stones are a common condition, but PH3 should be considered in cases with recurring stones or other systemic symptoms.
• Nephrocalcinosis: Excessive calcium deposits in the kidneys can occur in various conditions, including PH3.
• Chronic Kidney Disease (CKD): Reduced kidney function can be a feature of PH3, but it's also common in other kidney disorders.

Key Diagnostic Features to Distinguish PH3:

• Genetic Testing: Identifying mutations in the HOGA1 gene, which codes for the mitochondrial 4-hydroxy-2-oxoglutarate aldolase enzyme, is crucial for diagnosing PH3.
• Metabolic Testing: Measuring urinary oxalate levels and plasma oxalate concentrations can help differentiate PH3 from other conditions.

References:

[7] Identifies PH3 as a rare autosomal recessive disorder of glyoxylate metabolism. [13] Discusses the primary hyperoxalurias (PHs) as inborn errors of metabolism that result in hepatic overproduction of oxalate. [14] Mentions PH1, 2, and 3 as rare autosomal recessive disorders of glyoxylate metabolism resulting in hepatic overproduction of oxalate.

[12] Localizes the genetic defect in PH3 to the HOGA1 gene on chromosome 9, which codes for the mitochondrial 4-hydroxy-2-oxoglutarate aldolase enzyme. [15] Discusses differential diagnosis and secondary hyperoxaluria, including conditions that can mimic primary hyperoxaluria.

[10] Mentions PH3 as a recently described entity occurring in 10% of PH cases.