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Primary Hyperoxaluria

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Description: Primary hyperoxaluria is a rare genetic disorder that causes the liver to produce an excessive amount of oxalate, leading to kidney stones and potentially kidney failure.
Type: Primary hyperoxaluria is inherited in an autosomal recessive manner.
Signs And Symptoms: ### Primary Hyperoxaluria

**Signs and Symptoms:**
- Recurrent kidney stones
- Blood in the urine (hematuria)
- Frequent urinary tract infections
- Pain in the lower back or abdomen
- Reduced kidney function leading to chronic kidney disease
- Oxalate crystals in the kidneys, urine, and other tissues

Primary hyperoxaluria is a rare genetic disorder causing excessive production of oxalate, which can accumulate and lead to kidney stones and other serious health issues.
Prognosis: Primary hyperoxaluria is a rare genetic condition characterized by the overproduction of oxalate, leading to kidney stones and renal failure. The prognosis varies depending on the type and severity of the disease. Early diagnosis and management are crucial to prevent or slow the progression of kidney damage. With proper treatment, including hydration, medication, and sometimes liver or kidney transplantation, the prognosis can improve significantly, but the condition still often leads to end-stage renal disease if not adequately managed. Advanced cases may have a poorer outlook.
Onset: Primary hyperoxaluria typically presents in infancy or early childhood. However, symptoms can sometimes be delayed until adolescence or even adulthood. The primary symptom is usually recurrent kidney stones or nephrocalcinosis.
Prevalence: Primary hyperoxaluria is a rare genetic disorder with an estimated prevalence of 1 to 3 cases per 1 million people.
Epidemiology: Primary hyperoxaluria refers to a rare group of inherited metabolic disorders characterized by the overproduction of oxalate. Epidemiologically, the incidence rates of primary hyperoxaluria (PH) are estimated at about 1 to 3 cases per million people annually. The condition is more commonly diagnosed in individuals of European descent, although it can occur in any ethnic group. There are three main types of primary hyperoxaluria (PH1, PH2, and PH3), with Type 1 (PH1) being the most severe and most common. PH1 alone accounts for approximately 80% of cases. The prevalence of all types combined is estimated to be about 1 to 3 per 100,000 people.
Intractability: Primary hyperoxaluria is a rare and often severe genetic disorder characterized by the overproduction of oxalate, which can lead to kidney stones, kidney damage, and other systemic issues. While it is challenging to manage and can lead to serious complications, it is not necessarily intractable. Treatment options, including medications, dietary modifications, and in some cases, organ transplantation, can help manage symptoms and improve quality of life. Advances in gene therapy and other research are ongoing, aiming to provide more effective treatments in the future.
Disease Severity: Primary hyperoxaluria is a rare genetic disorder that can cause severe health issues, including kidney stones, kidney failure, and systemic oxalosis, which can lead to organ damage. The severity of the disease can vary significantly among individuals, ranging from mild symptoms to life-threatening complications.
Healthcare Professionals: Disease Ontology ID - DOID:2977
Pathophysiology: Primary hyperoxaluria is a rare genetic disorder characterized by the overproduction of oxalate, a substance that normally binds with calcium and is excreted in the urine. The pathophysiology of this condition involves defects in specific liver enzymes, most commonly:

1. **PH1 (Primary Hyperoxaluria Type 1)**: Caused by mutations in the AGXT gene leading to deficient activity of the enzyme alanine-glyoxylate aminotransferase (AGT). This defect results in the accumulation of glyoxylate, which is converted to oxalate.

2. **PH2 (Primary Hyperoxaluria Type 2)**: Results from mutations in the GRHPR gene, which impairs glyoxylate reductase/hydroxypyruvate reductase (GRHPR) activity. This leads to excessive conversion of glyoxylate into oxalate.

3. **PH3 (Primary Hyperoxaluria Type 3)**: Linked to mutations in the HOGA1 gene affecting the enzyme 4-hydroxy-2-oxoglutarate aldolase (HOGA), contributing to increased oxalate production.

Elevated oxalate levels cause it to combine with calcium, forming insoluble calcium oxalate crystals that can accumulate in the kidneys and other tissues, leading to kidney stones, nephrocalcinosis, and eventually renal failure if untreated.
Carrier Status: Primary hyperoxaluria is an autosomal recessive genetic disorder. This means that carriers of the condition typically have one mutated copy of the gene and one normal copy. Carriers usually do not exhibit symptoms but have a risk of passing the gene to their offspring. If both parents are carriers, there is a 25% chance with each pregnancy that the child will inherit two mutated copies and have the disease.
Mechanism: Primary hyperoxaluria (PH) is a rare genetic disorder characterized by the overproduction of oxalate due to defects in specific liver enzymes involved in glyoxylate metabolism. The excess oxalate combines with calcium to form kidney stones and can lead to kidney failure.

### Mechanism:
PH results from a deficiency in one of the enzymes responsible for processing glyoxylate, a metabolic intermediate. This leads to the accumulation of glyoxylate, which is subsequently converted to oxalate. The excess oxalate cannot be efficiently excreted by the kidneys, resulting in its accumulation and the formation of calcium oxalate crystals that can damage the kidneys and other tissues.

### Molecular Mechanisms:
1. **Type 1 PH (PH1)**: Caused by mutations in the AGXT gene, which encodes the enzyme alanine-glyoxylate aminotransferase (AGT). AGT is primarily found in liver peroxisomes and facilitates the conversion of glyoxylate to glycine, preventing the formation of oxalate. Mutations in AGXT lead to AGT enzyme deficiency or dysfunction, causing an increase in oxalate production.

2. **Type 2 PH (PH2)**: Linked to mutations in the GRHPR gene, which encodes glyoxylate reductase/hydroxypyruvate reductase (GRHPR). This enzyme converts glyoxylate to glycolate and hydroxypyruvate to D-glycerate. Mutations in GRHPR result in reduced conversion of glyoxylate, leading to its accumulation and subsequent conversion to oxalate.

3. **Type 3 PH (PH3)**: Associated with mutations in the HOGA1 gene, which encodes 4-hydroxy-2-oxoglutarate aldolase (HOGA). HOGA is involved in the breakdown of hydroxyproline into glyoxylate. Mutations in HOGA1 disturb this pathway, causing elevated glyoxylate and oxalate levels.

These molecular defects disrupt normal metabolic pathways in the liver, leading to the overproduction of oxalate, which can crystallize with calcium and cause kidney stones and renal damage.
Treatment: The main therapeutic approach to primary hyperoxaluria is still restricted to symptomatic treatment, i.e. kidney transplantation once the disease has already reached mature or terminal stages. However, through genomics and proteomics approaches, efforts are currently being made to elucidate the kinetics of AGXT folding which has a direct bearing on its targeting to appropriate subcellular localization. A child with primary hyperoxaluria was treated with a liver and kidney transplant. A favorable outcome is more likely if a kidney transplant is complemented by a liver transplant, given the disease originates in the liver.
Secondary hyperoxaluria is much more common than primary hyperoxaluria, and should be treated by limiting dietary oxalate and providing calcium supplementation.
Compassionate Use Treatment: Primary hyperoxaluria is a rare genetic condition characterized by the overproduction of oxalate, which can lead to kidney stones and renal failure. For compassionate use, off-label, or experimental treatments:

1. **Lumasiran**: An RNA interference therapy targeting the enzyme alanine-glyoxylate aminotransferase (AGT). It is approved for primary hyperoxaluria type 1 (PH1) but can be considered for compassionate use in certain cases.

2. **Allogeneic Liver Transplantation**: It is the definitive treatment for patients with PH1 as it addresses the underlying enzymatic defect but remains an option for end-stage disease due to its invasiveness and risk.

3. **Oxalobacter formigenes**: This is a bacterium that degrades oxalate in the gut, and its administration is being explored as a potential treatment to reduce oxalate levels in primary hyperoxaluria patients.

4. **Dicerna Pharmaceuticals' Nedosiran (DCR-PHXC)**: An investigational RNAi therapeutic aimed at reducing oxalate production, currently in clinical trials.

5. **Dietary and Pharmacological Approaches**: Low-oxalate diets, increased fluid intake, and drugs such as pyridoxine (vitamin B6) may be used off-label to help manage symptoms, particularly in milder forms or as adjunctive therapy.

These treatments and approaches aim to manage oxalate levels, prevent kidney damage, and improve patient outcomes.
Lifestyle Recommendations: For primary hyperoxaluria, lifestyle recommendations typically include:

1. **Hydration:** Maintaining high fluid intake to help dilute and excrete oxalate in urine.
2. **Dietary Modifications:** Restricting foods high in oxalate such as spinach, nuts, and beets.
3. **Calcium Intake:** Ensuring adequate calcium intake during meals to bind oxalate in the gut and reduce its absorption.
4. **Avoiding High Vitamin C:** Limiting intake of high doses of vitamin C, which can increase oxalate production.
5. **Regular Monitoring:** Frequent check-ups with a healthcare provider to monitor kidney function and oxalate levels.
6. **Medications:** Following prescribed treatments to reduce oxalate production and kidney damage.

These recommendations should be personalized based on individual medical advice.
Medication: Currently, no medications exist specifically labeled "nan" for treating primary hyperoxaluria. However, treatments for primary hyperoxaluria include:

1. **Hydration and Diet:**
- High fluid intake to dilute urine and reduce oxalate concentration.
- Dietary modifications to limit oxalate intake.

2. **Medications:**
- **Pyridoxine (Vitamin B6):** Can reduce oxalate production in certain patients.
- **Alkaline citrate or potassium citrate:** To inhibit calcium oxalate crystal formation.
- **Oxalobacter formigenes:** Probiotics aimed at breaking down oxalate in the gut.

3. **Gene Therapy and RNA Interference:**
- **Lumasiran:** An FDA-approved RNA interference therapeutic that targets the HAO1 gene to reduce oxalate production.

4. **Other Treatments:**
- Hemodialysis or peritoneal dialysis for advanced cases to remove oxalates from blood.
- Liver and kidney transplantation in severe cases.

Always consult a healthcare professional for the most appropriate treatment plan for primary hyperoxaluria.
Repurposable Drugs: Primary hyperoxaluria is a rare genetic disorder characterized by the overproduction of oxalate, which can lead to kidney stones and renal failure. Currently, repurposable drugs for this condition are still under investigation. However, findings have suggested that pyridoxine (vitamin B6) may reduce oxalate production in some patients with primary hyperoxaluria, particularly those with type 1. Other potential therapeutic approaches involve the use of inhibitors that target the glycolate oxidase enzyme (e.g., setanaxib), but these are primarily under clinical research stages.
Metabolites: Primary hyperoxaluria is a rare genetic disorder characterized by the overproduction of oxalate, which leads to the formation of kidney stones and other complications. The main metabolite involved in this disorder is oxalate. Elevated levels of glycolate and glyoxylate are also commonly observed in individuals with certain types of primary hyperoxaluria.
Nutraceuticals: Nutraceuticals are not typically a primary treatment for primary hyperoxaluria. This rare genetic disorder causes the liver to produce an excessive amount of oxalate, leading to kidney stones and potential renal failure. While dietary management, including avoiding high-oxalate foods, is recommended, the use of nutraceuticals specifically to manage this condition is not well established. It's essential for patients to consult healthcare providers for appropriate medical therapies, which may include medications to reduce oxalate production or even liver and kidney transplantation in severe cases.
Peptides: In the context of primary hyperoxaluria, any reference to "peptides" would likely pertain to the proteins and enzymes involved in the metabolic pathways affected by the condition. Primary hyperoxaluria is a rare genetic disorder that results in the overproduction of oxalate, which can combine with calcium to form kidney stones and other complications. Specific enzymes like alanine-glyoxylate aminotransferase (AGT), glyoxylate reductase/hydroxypyruvate reductase (GRHPR), and 4-hydroxy-2-oxoglutarate aldolase (HOGA) are critical in these metabolic pathways. Mutations in the genes encoding these enzymes can disrupt their normal function, leading to the disease.

Nan ("not applicable" or "not available") could imply a data field where information on peptides specific to primary hyperoxaluria is not provided or not relevant for the intended inquiry. However, advancements in peptide-based therapies and nanotechnologies are areas of ongoing research, including potential applications for genetic and metabolic disorders like primary hyperoxaluria.

If you are interested in specific peptides or therapeutic advances, further specialized sources or current research literature may provide more detailed insights.