xanthinuria

Xanthinuria: A Rare Genetic Disorder

Xanthinuria is a rare genetic disorder characterized by a deficiency of the xanthine dehydrogenase/oxidase enzyme, leading to very low levels of uric acid and high concentrations of xanthine in the blood and urine [5]. This condition affects the kidneys and can cause various symptoms, including:

• High levels of xanthine in the urine
• Low levels of uric acid in the blood and urine
• Urolithiasis (formation of kidney stones) due to high concentrations of xanthine in the urine [9]

Xanthinuria is classified into two types: XAN1 and XAN2. Type I is caused by a deficiency of the xanthine dehydrogenase/oxidase enzyme, while Type II is an autosomal recessive condition resulting from a defect in the synthesis of the molybdenum cofactor [4].

The symptoms of xanthinuria can vary depending on the type and severity of the condition. In some cases, it may not cause any noticeable symptoms until later in life.

References:

• [1] Dec 1, 2015 — It is characterized by high levels of a compound called xanthine and very low levels of another compound called uric acid in the blood and urine ...
• [3] Dec 1, 2015 — Hereditary xanthinuria is a condition that most often affects the kidneys. It is characterized by high levels of a compound called xanthine and ...
• [5] Xanthinuria is a rare genetic disorder caused by a deficiency of the xanthine dehydrogenase/oxidase enzyme, leading to very low levels of uric acid and high ...
• [9] It is characterized by low concentrations of uric acid in blood and urine and high concentrations of xanthine in urine, which produces urolithiasis. Xanthinuria ...

Xanthinuria is a rare genetic disorder that affects the metabolism of purines, leading to the formation of kidney stones and other complications. The signs and symptoms of xanthinuria can vary in severity and may include:

• Kidney stones: One of the most common symptoms of xanthinuria is the formation of kidney stones, which can impair kidney function and ultimately cause kidney failure [1][2].
• Urinary tract infections (UTIs): Approximately 50% of patients with classical hereditary xanthinuria present with symptoms of UTIs, such as pain or burning during urination [2].
• Blood in the urine (hematuria): Related signs and symptoms can include blood in the urine, which may be a sign of kidney damage or disease [3][7].
• Abdominal pain: Abdominal pain is another common symptom of xanthinuria, which can range from mild to severe [1][4].
• Muscle cramps and pain: Muscle cramps, pain, or tightness in the hands, legs, or jaw are also reported manifestations of xanthinuria, particularly after vigorous exercise [5].
• Joint pain and swelling: Some patients may experience joint pain and swelling, which can be a sign of underlying metabolic disorders [5].
• Renal failure: In severe cases, xanthinuria can lead to renal failure, which is a life-threatening condition that requires immediate medical attention [1][8].

It's essential to note that the symptoms of xanthinuria can vary in severity and may not be present at birth. Some patients may experience symptoms later in life, while others may remain asymptomatic until adulthood.

References: [1] Dec 1, 2015 — These stones can impair kidney function and ultimately cause kidney failure. [2] Symptom onset may be at any age. Approximately 50 % of the patients with classical hereditary xanthinuria present with symptoms of urinary tract infection... [3] Dec 30, 2020 — Other reported manifestations include severe metabolic acidosis and intracranial hemorrhage. [4] Dec 1, 2015 — These stones can impair kidney function and ultimately cause kidney failure. Related signs and symptoms can include abdominal pain, recurrent ... [5] Dec 30, 2020 — The symptoms may include muscle cramps, pain, or tightness in the hands, legs, or jaw. Muscle pain can follow vigorous exercise. [6] Xanthinuria is a rare autosomal recessive disorder of purine metabolism that leads to urolithiasis. [7] Related signs and symptoms can include abdominal pain, recurrent urinary tract infections, and blood in the urine (hematuria). Less commonly, xanthine crystals ... [8] What are the signs and symptoms? · Kidney stones · Renal failure · Renal cysts · Urinary tract infections · Large intestine ulceration · Floppy head due to xanthine ...

Diagnostic Tests for Xanthinuria

Xanthinuria, also known as hereditary xanthinuria, is a rare genetic disorder that affects the kidneys and leads to excessive excretion of xanthine in the urine. Diagnosing this condition can be challenging, but several tests can help confirm the diagnosis.

• Measurement of Uric Acid: The first step in diagnosing xanthinuria is to measure uric acid levels in blood and urine. If hypouricemia (low uric acid levels) is confirmed, further investigation into purine metabolism follows [4].
• Allopurinol Loading Test: This test has been traditionally used to differentiate between HX types I and II. However, the results of this test should be interpreted with caution, as they may not always accurately reflect the underlying condition [2].
• High-Performance Liquid Chromatography (HPLC): This method can be employed for the detection of urinary xanthine, hypoxanthine, and other purines. It provides a quantitative report of these substances in urine [7].
• Blood Test: A blood test alongside the expression of signs and symptoms associated with this condition may also help diagnose xanthinuria [8].

Other Diagnostic Tests

In addition to the above tests, other diagnostic methods may be employed to confirm the diagnosis of xanthinuria. These include:

• Imaging Studies: Imaging studies such as X-rays or CT scans may be used to rule out other conditions that may cause similar symptoms.
• Histologic Findings: Histological examination of kidney tissue may also provide clues about the underlying condition.

References

[1] Dec 30, 2020 — Laboratory clues that may suggest the diagnosis of xanthinuria include a radiolucent stone, low serum and urine uric acid levels, or crystal nephropathy of ...

[2] by M Mraz · 2015 · Cited by 48 — The allopurinol loading test has been traditionally used to differentiate between HX types I and II. Final confirmation of HX has been based on the biopsy ...

[3] Dec 1, 2015 — Hereditary xanthinuria is a condition that most often affects the kidneys. Explore symptoms, inheritance, genetics of this condition.

[4] Diagnosis is based on the measurement of uric acid in blood and urine. If hypouricemia is confirmed, detailed purine metabolic investigation follows, and ...

[5] Dec 30, 2020 — Physical Examination · Show All · DDx; Workup. Laboratory Studies · Imaging Studies · Other Tests · Histologic Findings · Show All. Treatment.

[6] Hereditary xanthinuria is an autosomal recessive genetic disorder that results in excessive xanthine (a metabolic byproduct) in the urine.

[7] by N Akıncı · 2013 · Cited by 16 — However, levels of hypoxanthine, and xanthine can be measured using high-performance liquid chromatographic (HPLC) methods employed for the detection of urinary ...

[8] Therefore this may also be diagnosed via a blood test alongside the expression of signs and symptoms that are associated with this condition. Can it be treated?

Treatment Options for Xanthinuria

Xanthinuria, a rare genetic disorder characterized by the inability to break down purines, can be managed through various treatment options.

• Allopurinol: This medication is often used to treat xanthinuria. Allopurinol works by inhibiting the enzyme xanthine oxidase, which is responsible for converting hypoxanthine and xanthine into uric acid. By blocking this enzyme, allopurinol helps reduce the levels of xanthine in the urine.
• Cyclic Pyranopterin Monophosphate (cPMP): This biosynthetic precursor of the cofactor is used to treat molybdenum cofactor deficiency (MoCD), a condition that can lead to xanthinuria. cPMP helps restore normal purine metabolism and reduce xanthine levels in the urine.
• Aldehyde Oxidase Inhibitors: These medications can also be used to manage xanthinuria by inhibiting the enzyme aldehyde oxidase, which is involved in the degradation of azathioprine or

Differential Diagnosis of Xanthinuria

Xanthinuria, also known as xanthine oxidase deficiency, is a rare genetic disorder that can be challenging to diagnose due to its similarity with other conditions. The differential diagnosis for xanthinuria involves ruling out other disorders that may present with similar symptoms.

• Molybdenum cofactor deficiency: This condition shares clinical features with hereditary xanthinuria and should be considered in the differential diagnosis [1].
• Allopurinol loading test: An allopurinol loading test can help determine if the drug is oxidized by AOX1 to oxipurinol, which is essential for diagnosing classical type II xanthinuria [6].
• Xanthine oxidase deficiency: This condition is a rare genetic disorder that causes the accumulation of xanthine and should be considered in the differential diagnosis of xanthinuria [7].

Key Points to Consider

• Xanthinuria is a rare genetic disorder caused by a deficiency of the xanthine dehydrogenase/oxidase enzyme.
• The condition leads to very low levels of uric acid and high levels of hypoxanthine and xanthine in the urine.
• Differential diagnosis for classical type II xanthinuria includes an allopurinol loading test.

References

[1] Context 1: Hereditary xanthinuria is a clinical feature of molybdenum cofactor deficiency (see this term). [4] Symptoms of XOR Deficiency and Differential Diagnosis. Human diseases associated with genetic dysfunction of XOR are termed xanthinuria, because xanthine is ... [6] The differential diagnosis for classical type II xanthinuria is an allopurinol loading test to determine if the drug is oxidized by AOX1 to oxipurinol (Ichida ...). [7] Xanthinuria, also known as xanthine oxidase deficiency, is a rare genetic disorder causing the accumulation of xanthine. It is caused by a deficiency of the ... [8] Xanthinuria is a rare genetic disorder caused by a deficiency of the xanthine dehydrogenase/oxidase enzyme, leading to very low levels of uric acid and high ...