Summary about Disease
Oxalosis, also known as primary hyperoxaluria (PH), is a rare, inherited metabolic disorder characterized by the overproduction of oxalate by the liver. This excess oxalate leads to the formation of calcium oxalate crystals that deposit in the kidneys and other organs, causing kidney damage, kidney stones, and eventually systemic oxalosis affecting the heart, bones, eyes, and other tissues. There are three main types of PH: PH1, PH2, and PH3, each caused by different gene mutations affecting different enzymes in the oxalate production pathway.
Symptoms
Symptoms vary in severity and age of onset. Common symptoms include:
Kidney stones (nephrolithiasis)
Kidney failure (renal insufficiency)
Blood in the urine (hematuria)
Urinary tract infections
Bone pain
Joint pain
Anemia
Cardiac problems (arrhythmias, cardiomyopathy)
Eye problems (retinopathy)
Skin rashes
Causes
Oxalosis is caused by genetic mutations in genes that control the production of oxalate in the liver.
PH1: Mutations in the AGXT gene, which encodes the enzyme alanine-glyoxylate aminotransferase (AGT).
PH2: Mutations in the GRHPR gene, which encodes the enzyme glyoxylate reductase/hydroxypyruvate reductase (GRHPR).
PH3: Mutations in the HOGA1 gene, which encodes the enzyme 4-hydroxy-2-oxoglutarate aldolase (HOGA1). These mutations lead to a deficiency or malfunction of these enzymes, resulting in the overproduction of oxalate.
Medicine Used
Treatment aims to reduce oxalate production and prevent crystal formation. Common medications include:
High fluid intake: To dilute urine and flush out oxalate.
Potassium citrate: To increase urine pH and inhibit crystal formation.
Pyridoxine (Vitamin B6): May be effective in some patients with PH1 to reduce oxalate production.
Phytate: To inhibit calcium oxalate crystal growth.
Liver transplantation: In severe cases of PH1, a liver transplant can correct the metabolic defect and reduce oxalate production.
Kidney transplantation: May be necessary if kidney failure develops, but it is often done in conjunction with a liver transplant to prevent recurrence of oxalosis in the new kidney.
Lumasiran (Oxlumo): An RNAi therapeutic that reduces hepatic oxalate production by targeting the HAO1 gene in PH1.
Nedosiran (Rivfloza): An RNAi therapeutic that reduces hepatic oxalate production by targeting the LDHA gene and is being tested for use in all types of Primary Hyperoxaluria.
Is Communicable
No, oxalosis is not communicable. It is a genetic disorder and cannot be spread from person to person.
Precautions
Precautions focus on managing the disease and preventing complications:
Adherence to treatment: Follow the prescribed medication regimen and dietary recommendations.
High fluid intake: Drink plenty of water throughout the day.
Regular monitoring: Undergo regular blood and urine tests to monitor oxalate levels and kidney function.
Dietary modifications: Follow a low-oxalate diet, avoiding foods high in oxalate such as spinach, rhubarb, nuts, chocolate, and tea.
Genetic counseling: For families with a history of oxalosis, genetic counseling can help assess the risk of passing the condition on to their children.
How long does an outbreak last?
Oxalosis is not characterized by outbreaks. It is a chronic condition that requires lifelong management. The progression of the disease and the severity of symptoms vary depending on the type of PH, the age of onset, and the effectiveness of treatment.
How is it diagnosed?
Diagnosis involves a combination of clinical evaluation, laboratory tests, and genetic testing:
Urine oxalate measurement: Elevated levels of oxalate in the urine are a key diagnostic indicator.
Blood tests: To assess kidney function (creatinine, BUN) and oxalate levels.
Kidney stone analysis: To determine the composition of kidney stones (calcium oxalate).
Kidney biopsy: May be necessary to confirm oxalate crystal deposition in the kidneys.
Liver biopsy: May be performed to assess the activity of the enzymes involved in oxalate metabolism.
Genetic testing: To identify mutations in the AGXT, GRHPR, or *HOGA1* genes.
Timeline of Symptoms
The timeline of symptoms varies depending on the type and severity of PH:
Infancy/early childhood: Some individuals may present with kidney stones, hematuria, or kidney failure in infancy or early childhood.
Childhood/adolescence: Others may develop symptoms later in childhood or adolescence.
Adulthood: In rare cases, symptoms may not appear until adulthood. The progression of the disease can vary, with some individuals experiencing rapid kidney damage and others progressing more slowly.
Important Considerations
Early diagnosis and treatment are crucial to prevent or delay kidney damage and systemic complications.
Liver transplantation is a potentially curative treatment for severe PH1.
Kidney transplantation may be necessary but is often performed in conjunction with liver transplantation to prevent recurrence of oxalosis.
Clinical trials are ongoing to evaluate new therapies for oxalosis.
Patients with oxalosis require lifelong monitoring and management by a team of specialists, including nephrologists, urologists, and geneticists.