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Primary Hyperoxaluria Type II - Diagnostic Features, Adverse Health Effects, and Treatment

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Primary hyperoxaluria type II often manifests in childhood. Read below to learn more about primary hyperoxaluria type II.

Written byDr. Abhigya Sharma

Medically reviewed byDr. Yash Kathuria

Published At May 2, 2023
Reviewed AtSeptember 27, 2023

Introduction:

Primary hyperoxaluria type 2 (PH2) often manifests in childhood, with patients diagnosed later in life frequently citing childhood symptoms. Similar to PH1, diagnosis is frequently postponed, sometimes for years.

The symptoms that are currently present are often those that are linked to the presence of kidney stones, such as hematuria, renal colic, or urinary blockage. End-stage renal disease (ESRD) may also be evident in those affected. The majority of people have calcium oxalate-based kidney stones.

Compared to PH1, ESRD is significantly less frequently seen on ultrasound, abdomen x-ray, or CT examination in PH2. Although this outcome occurs later in PH2 than in PH1, 50% of affected people have ESRD by 25. The disease can progress to this stage. 20 % of those with PH2 who had follow-up data obtained got ESRD.

What Are the Diagnostic Features of Primary Hyperoxaluria Type II?

The following clinical and laboratory characteristics in patients should raise suspicions of primary hyperoxaluria type 2 (PH2):

Clinical Findings:

  • Nephrolithiasis signs and symptoms (e.g., hematuria, renal colic, and urinary tract obstruction).

  • Nephrolithiasis that recurs frequently.

  • Nephrocalcinosis.

  • History of nephrolithiasis along with end-stage renal disease.

Laboratory Findings:

  • Study of kidney stones. Kidney stones are primarily made of calcium oxalate. Therefore, an acid 24-hour collection is more effective than a random sample.

What Are the Adverse Health Effects of Primary Hyperoxaluria Type II?

The following are the adverse health effects of PH2:

Oxalosis: Once ESRD develops, oxalate deposition can happen in organs besides the kidney, such as bone, bone marrow, joints, the retina, and the heart.

Transverse translucent symmetric bands with permanent sclerotic edges at the ends of long bones are seen on x-rays due to oxalate deposition in bone, and the bones after that undergo cystic rarefaction. In severe illness, osteodystrophy results in many pathologic fractures and bone discomfort. A bone marrow involvement can cause anemia that is resistant to erythropoietin-stimulating drugs. Additional clinical signs of oxalosis may include cardiomyopathy, retinopathy, and maculopathy, as well as visual disruption brought on by these conditions. Periodontal disease is one of the dental problems. There are also reports of hypothyroidism.

Hereditary Causes of Kidney Stones: Dent disease and renal tubular acidosis are two more heritable conditions that manifest with early stone development. It is crucial to study the stone in patients with renal stone disease symptoms since doing so can assist the doctor in deciding which course of action to take. The urine analysis should determine urine volume, oxalate, calcium, magnesium, citrate, phosphate, sodium, and urate and a risk profile for kidney stones.

End-Stage Renal Disease: It is impossible to evaluate urine oxalate excretion in patients with ESRD accurately. Any ESRD can cause plasma oxalate increases up to 40 mol/L; plasma oxalate concentrations over 50 mol/L indicate primary hyperoxaluria. While PH1 and PH2 are uncommon causes of ESRD in adults, PH can cause 0.7% to 1.6% of ESRD in children. PH should be considered in a native kidney or renal allograft biopsy if birefringent crystals are visible under polarized light. Although plasma L-glycerate measurements can identify people with PH2 who have ESRD, such testing is not frequently available. A liver biopsy or molecular genetic testing of key enzymes is needed for a conclusive diagnosis.

Enteric Hyperoxaluria: Hyperoxaluria may result from gastrointestinal tract disorders that cause malabsorption, such as celiac disease, Crohn's disease, pancreatitis, and short bowel syndrome; however, these conditions are typically excluded based on a patient's medical history. Increased oxalate absorption, high levels of hyperoxaluria, and an increased risk of kidney stone development have all been linked to gastric bypass surgery. People with gastric bypass experience urinary risk factors for stones more frequently than those with gastric bandings, such as hyperoxaluria.

Dietary Hyperoxaluria: Excessive consumption of oxalate-rich foods, such as chocolate, cocoa, leafy greens (particularly rhubarb and spinach), black tea, almonds, peanut butter, or starfruit, may raise the level of oxalate in the urine. Oxalate from food accounts for between 24 % and 53 % of the oxalate in the urine. Treatment involves limiting dietary oxalate intake and using calcium carbonate or calcium citrate to bind dietary oxalate during meals. Hypercalciuria has been caused by excessive vitamin C intake (4 g/day) and intentional or unintentional use of ethylene glycol.

What Is the Treatment Given for Primary Hyperoxaluria Type II?

The following evaluations, originally suggested for PH1, are recommended to determine the degree of disease in a person with primary hyperoxaluria type 2 (PH2):

  • Evaluation of renal function.

  • Evaluation of systemic oxalate deposition in tissue and bone if moderate-to-advanced ESRD is present.

  • Bone cystic rarefaction is done after taking bone x-rays to look for radio dense metaphyseal bands.

  • Examining the retina with an ophthalmologist to check for oxalate crystals.

  • Echocardiography and EKG evaluation of heart function.

  • Clinical geneticist and genetic counselor consultation.

Dialysis:

Early dialysis or kidney transplantation is desirable since the plasma oxalate concentration rises when the renal clearance is less than 40 mL/min.

Hemodialysis results in a higher clearance of oxalate than peritoneal dialysis. To improve total oxalate clearance and lessen rebound following hemodialysis, a mix of intermittent daily hemodialysis, overnight peritoneal dialysis, or severe home hemodialysis is used. These combination therapies have all been recommended to enhance oxalate removal, whether they involve high flux dialyzers or lengthy hemofiltration sessions. To maximize oxalate elimination for people with ESRD, intensive (daily) dialysis is necessary. As with PH1, systemic oxalate deposition is more likely to occur the longer the patient with PH2 is on dialysis.

Organ Transplantation:

With various degrees of success, kidney transplantation alone has been utilized in PH2. Allograft loss due to oxalate deposition can be reduced with careful postoperative treatment, attention to vigorous urine flow, and using calcium oxalate urinary inhibitors. The combination liver-kidney transplant may have some benefits because it is not uncommon for such transplants to fail in people with PH2 and because the liver contains more enzymes than other organs.

There has only ever been one successful liver-kidney transplant in a patient with PH2 who had previously experienced a failed renal allograft. Within one month of the transplant, the urine glycerate, oxalate, and plasma oxalate levels all returned to normal. They stayed normal for the 13-month follow-up.

Conclusion:

In summary, primary hyperoxaluria type II is a rare genetic illness that impairs the body's capacity to correctly metabolize oxalate, causing oxalate crystals to accumulate in a number of organs. Serious health issues like kidney impairment and harm to other organs may occur from this. Early detection and intervention are essential for controlling the illness and averting permanent harm. Whilst there isn't a solution for Primary Hyperoxaluria Type at the moment, continuous studies and advances in medicine give hope for better treatment choices in the future.

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Frequently Asked Questions

An insufficiency of the enzyme alanine-glyoxylate aminotransferase (AGT) results in primary hyperoxaluria type 1, which is characterized by a buildup of oxalate mostly in the urine and kidneys. On the other hand, glyoxylate reductase/hydroxypyruvate reductase (GRHPR) deficiency causes primary hyperoxaluria type 2, which causes a similar accumulation of oxalate but with extra excretion of glyoxylate and hydroxypyruvate.

One mutated copy of the GRHPR gene is inherited by the hereditary carrier of primary hyperoxaluria type 2, who usually shows no symptoms but can pass the mutation on to their progeny. This mutation contributes to the inheritance pattern of the illness by causing a deficit in the enzyme glyoxylate reductase or hydroxypyruvate reductase (GRHPR).

Primary hyperoxaluria is classified into three forms: type 1, type 2, and type 3. These types are caused by mutations in various genes related to the metabolism of oxalate. The upshot of these mutations is an accumulation of oxalate in the body due to different defects in enzymes that are essential for the breakdown of oxalate.

A lack of the enzyme alanine-glyoxylate aminotransferase (AGT) is seen in primary hyperoxaluria. This inadequacy causes the body to retain more oxalate, which exacerbates kidney stones and other associated problems.

Elevated urine oxalate levels, recurring kidney stones, nephrocalcinosis (calcium deposits in the kidneys), and gradual renal impairment are the hallmarks of primary hyperoxaluria.

The frequency of primary hyperoxaluria type 2, a rare hereditary condition, is thought to be 1 in 1,000,000 people globally. Compared to primary hyperoxaluria type 1, it is far less common.

The development of enzyme replacement medicines, such as lumasiran, which targets the liver enzyme glycolate oxidase to lower oxalate formation, is one recent improvement in the treatment of primary hyperoxaluria. Furthermore, the use of gene editing and RNA (Ribonucleic acid) interference techniques in gene therapy holds promise for rectifying the genetic abnormalities causing primary hyperoxaluria.

Although there is no cure for primary hyperoxaluria, there are effective management strategies that attempt to lower oxalate production and avoid kidney injury. These therapies consist of dietary changes, enzyme replacement therapy, and, in certain situations, kidney or liver transplants.

To lower oxalate levels and prevent kidney stone formation, drugs such as Pyridoxine, Calcium supplements, Allopurinol, and Cholestyramine are used to treat primary hyperoxaluria, a hereditary disease that causes an excess of oxalate to be produced. A low-oxalate diet and enough hydration are examples of lifestyle changes that support drug therapy in the treatment of primary hyperoxaluria.

The main cause of primary hyperoxaluria is a genetic mutation that causes an excess of oxalate, which is normally removed by the kidneys. These mutations impact the enzymes responsible for the metabolism of hydroxyproline or glyoxylate, which causes an overabundance of oxalate to be produced and consequent kidney stone formation.

Primary hyperoxaluria, enteric hyperoxaluria, and secondary hyperoxaluria resulting from disorders such as inflammatory bowel disease or bariatric surgery are additional factors to take into account when diagnosing hyperoxaluria. In a differential diagnosis, other kidney stone sources are ruled out and potential metabolic problems are evaluated.

Although it can occasionally appear in adolescence or maturity, primary hyperoxaluria usually first appears in infancy or early childhood. The particular genetic mutation at play will determine the age at which symptoms manifest.

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Dr. Yash Kathuria from iCliniq
Dr. Yash Kathuria

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