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primary hyperoxaluria

ICD-10 Codes

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Description

Primary Hyperoxaluria: A Rare Genetic Disorder

Primary hyperoxaluria (PH) is a rare genetic metabolic disorder characterized by the accumulation of oxalate in the kidneys and other organs [3]. It is primarily caused by autosomal recessive variants in three genes that encode enzymes involved in glyoxylate metabolism, leading to enhanced oxalate production [1].

Causes and Symptoms

The condition is caused by a deficiency of the liver peroxisomal enzyme alanine-glyoxylate aminotransferase (AGT), which catalyzes the conversion of glyoxylate to glycine. When AGT activity is reduced or absent, glyoxylate is converted to oxalate, which cannot be metabolized and must be excreted by the kidneys [2]. This leads to the formation of insoluble calcium oxalate crystals in the kidneys, causing kidney stones and potential kidney failure.

Types and Age of Onset

There are two main types of primary hyperoxaluria: type 1 (PH1) and type 2 (PH2). PH1 is caused by a deficiency of AGT, while PH2 is caused by mutations in the GRHPR gene. The age of onset for PH2 is typically in childhood, with symptoms often delayed until later life [15].

Complications and Diagnosis

If left untreated, primary hyperoxaluria can lead to recurrent kidney stones, nephrocalcinosis, and eventually end-stage renal disease (ESRD), a life-threatening condition that prevents the kidneys from filtering fluids and waste products from the body effectively [14]. Diagnosis is often delayed, sometimes even for years.

References

[1] Genetics — Primary hyperoxaluria (PH) is primarily caused by autosomal recessive variants in three genes that encode enzymes involved in glyoxylate metabolism. [2] Primary hyperoxaluria type 1 (PH1) is caused by deficiency of the liver peroxisomal enzyme alanine-glyoxylate aminotransferase (AGT). [3] Primary hyperoxaluria (PH) is a rare genetic metabolic disorder characterized by the accumulation of oxalate in the kidneys and other organs. [14] Primary hyperoxaluria is a rare condition characterized by recurrent kidney and bladder stones. [15] The age of onset of primary hyperoxaluria type 2 (PH2) is typically in childhood.

Additional Characteristics

  • Primary hyperoxaluria (PH) is a rare genetic metabolic disorder
  • characterized by the accumulation of oxalate in the kidneys and other organs
  • The condition is caused by a deficiency of the liver peroxisomal enzyme alanine-glyoxylate aminotransferase (AGT)
  • Type 1 (PH1) is caused by a deficiency of AGT, while Type 2 (PH2) is caused by mutations in the GRHPR gene
  • Primary hyperoxaluria can lead to recurrent kidney stones, nephrocalcinosis, and eventually end-stage renal disease (ESRD)
  • The age of onset for PH2 is typically in childhood

Signs and Symptoms

Primary hyperoxaluria (PH) is a rare genetic disorder that affects the liver, kidneys, and urinary tract. The signs and symptoms of PH can vary from person to person, but here are some common ones:

  • Kidney stones: One of the most common symptoms of PH is the formation of kidney stones, which can occur at any age, even in children [3][4][6]. These stones can be single or recurrent and may cause severe pain.
  • Pain in the low back, side, or lower abdomen: People with PH may experience pain in these areas due to the presence of kidney stones or other complications [4].
  • Blood in the urine: Some individuals with PH may have blood in their urine, which can be a sign of kidney damage or infection [5][9].
  • Urinary tract infections: Recurrent urinary tract infections (UTIs) are another common symptom of PH [8][9].
  • Failure to thrive: In some cases, children with PH may experience failure to thrive due to the disease's impact on their overall health [9].

It's essential to note that not everyone with PH will exhibit all these symptoms, and the severity can vary depending on the type of the disorder and individual factors. If you or a loved one is experiencing any of these signs and symptoms, it's crucial to consult a healthcare professional for proper diagnosis and treatment.

References:

[1] Context result 4 [2] Context result 5 [3] Context result 3 [4] Context result 4 [5] Context result 6 [8] Context result 8 [9] Context result 9

Additional Symptoms

  • Blood in the urine
  • Urinary tract infections
  • Kidney stones
  • Pain in the low back, side, or lower abdomen
  • failure to thrive

Diagnostic Tests

Diagnostic Tests for Primary Hyperoxaluria

Primary hyperoxaluria (PH) is a rare genetic disorder that affects the kidneys and urinary tract. Diagnosing PH requires a combination of clinical evaluation, laboratory tests, and genetic analysis.

Laboratory Tests:

  • Urine tests: These are used to measure levels of oxalate and other substances in the urine. A 24-hour urine collection is typically required to accurately assess oxalate levels [1].
  • DNA testing: This involves analyzing genes associated with PH, such as the AGXT gene, to identify genetic mutations that cause the condition [5].

Imaging Studies:

  • Kidney biopsy: This procedure involves taking a small sample of kidney tissue to examine for oxalate deposits and other signs of damage [3].
  • Bone marrow biopsy: In some cases, a bone marrow biopsy may be performed to assess for oxalate deposits in the bone marrow [3].

Other Diagnostic Tests:

  • Liver biopsy: A liver biopsy may be performed to evaluate for liver damage or disease associated with PH [3].
  • Genetic testing: This involves analyzing genes associated with PH to confirm a diagnosis and determine the specific type of PH (e.g., PH1, PH2) [4].

Diagnostic Workup:

A diagnostic workup in an individual with hyperoxaluria typically demonstrates increased concentration of oxalate in urinary metabolite screening. If glycolate, glycerate, or other substances are also elevated, it may indicate a specific type of PH [6]. The Invitae Primary Hyperoxaluria panel analyzes 3 genes associated with primary hyperoxaluria, which can help confirm a diagnosis and determine the disease type [7].

References:

[1] Context result 1 [2] Context result 10 [3] Context result 3 [4] Context result 4 [5] Context result 5 [6] Context result 8 [7] Context result 7

Treatment

Treatment Options for Primary Hyperoxaluria

Primary hyperoxaluria type 1 (PH1) is a rare genetic disorder characterized by excessive oxalate production, leading to kidney damage and failure. While there is no cure for PH1, various treatment options can help manage the condition and slow down its progression.

Medications

  • Pyridoxine (Vitamin B6): A prescription dose of pyridoxine has been shown to reduce oxalate levels in some patients with PH1 [7][9]. However, it does not always work and should be tried for at least 3 months to see if it helps.
  • Lumasiran (Oxlumo): In 2023, the U.S. Food and Drug Administration approved lumasiran as the first treatment for PH1 [5][6]. Lumasiran is an RNAi therapy that targets the AGXT gene responsible for PH1.

Other Treatments

  • Dialysis: A treatment called dialysis can help take over some of the work of your kidneys, but it doesn't keep up with the amount of oxalate your body makes [11].
  • Kidney Transplant or Kidney and Liver Transplant: In severe cases, a kidney transplant or kidney and liver transplant may be necessary to treat PH1. A liver transplant is the only treatment that might cure some types of primary hyperoxaluria [11].

Supportive Treatment

  • High Fluid Intake: Supportive treatment for PH1 focuses on high fluid intake and crystallization inhibitors [7][8]. This can help prevent kidney damage and slow down disease progression.

It's essential to note that each patient with PH1 is unique, and the most effective treatment plan may vary depending on individual circumstances. Consultation with a healthcare professional is necessary to determine the best course of action for managing PH1.

Recommended Medications

  • Pyridoxine (Vitamin B6)
  • Lumasiran (Oxlumo)

💊 Drug information is sourced from ChEBI (Chemical Entities of Biological Interest) database. Always consult with a healthcare professional before starting any medication. Click on any medication name for detailed information.

Differential Diagnosis

Differential Diagnosis of Primary Hyperoxaluria

Primary hyperoxaluria (PH) is a rare genetic disorder characterized by the overproduction of oxalate, leading to recurrent kidney stones, nephrocalcinosis, and potential kidney failure. When considering the differential diagnosis of PH, it's essential to take into account the three known causes of primary hyperoxaluria: type 1, type 2, and type 3 [1]. Additionally, other monogenic causes of stone diseases should be considered, as well as calcium oxalate stone disease of unknown cause [1].

Key Considerations

  • Primary Hyperoxaluria Type 1 (PH1): The most common form of inherited hyperoxaluria, accounting for approximately 80% of cases. PH1 is caused by a deficiency of the liver peroxisomal enzyme alanine:glyoxylate aminotransferase (AGT) [15].
  • Primary Hyperoxaluria Type 2 and 3: Less common forms of inherited hyperoxaluria, caused by biallelic pathogenic variants in GRHPR and HOGA1 genes, respectively [11].
  • Other Monogenic Causes of Stone Diseases: Conditions such as cystinuria, hypocitraturia, and hypercalciuria should be considered in the differential diagnosis [6].

Clinical Presentations

Patients with PH may present with kidney stones, nephrocalcinosis, and kidney failure of unknown etiology. Echogenic kidneys on ultrasound are a significant clinical finding that should prompt consideration of PH [12]. Prompt diagnosis is essential to prevent downstream complications, including advanced CKD or kidney failure at diagnosis [14].

References

[1] Context 1 [6] Context 6 [11] Context 11 [12] Context 12 [14] Context 14 [15] Context 15

Additional Information

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