adenine phosphoribosyltransferase deficiency

Adenine Phosphoribosyltransferase Deficiency: A Rare Metabolic Disorder

Adenine phosphoribosyltransferase (APRT) deficiency is a rare inherited metabolic disorder that affects the kidneys and urinary tract. This condition leads to the formation and hyperexcretion of 2,8-dihydroxyadenine (DHA) into urine [1][3][7]. The majority of symptomatic individuals with APRT deficiency experience recurrent 2,8-DHA kidney stones, abdominal pain, and/or urinary tract infections [4].

Causes and Symptoms

APRT deficiency is caused by mutations of the APRT gene, making it an autosomal recessive metabolic disorder [6][8]. The condition leads to a deficiency in the adenine phosphoribosyltransferase enzyme, which is essential for purine metabolism. This deficiency results in the accumulation of 2,8-DHA in the urine, causing kidney stones and other complications.

Complications and Treatment

The symptoms of APRT deficiency can range from mild to severe and may include recurrent kidney stones, abdominal pain, urinary tract infections, and progressive chronic kidney disease [5]. While there is no specific treatment for APRT deficiency, managing the condition through dietary changes and medications can help alleviate symptoms. In some cases, kidney transplantation may be necessary.

References

[1] Bollée G (2012) Adenine phosphoribosyltransferase deficiency: a rare inherited metabolic disorder [Context 1]

[3] Bollée G (2012) APRT deficiency is a rare inherited metabolic disorder that leads to the formation and hyperexcretion of DHA into urine [Context 7]

[4] The majority of symptomatic individuals with APRT deficiency experience recurrent 2,8-DHA kidney stones, abdominal pain and/or urinary tract infections [Context 4]

[5] Li J (2019) Adenine phosphoribosyltransferase enzyme deficiency is an important and potentially reversible cause of progressive chronic kidney disease [Context 5]

[6] Adenine phosphoribosyltransferase deficiency is a rare autosomal recessive metabolic disorder caused by mutations of the APRT gene [Context 6]

[7] Bollée G (2012) APRT deficiency is a rare inherited metabolic disorder that leads to the formation and hyperexcretion of DHA into urine [Context 3]

[8] Bollée G (2014) Adenine phosphoribosyltransferase (APRT) deficiency is a rare autosomal recessive disease leading to generation of large amounts of 2,8-dihydroxyadenine [Context 8]

Common Signs and Symptoms of Adenine Phosphoribosyltransferase Deficiency

Adenine phosphoribosyltransferase (APRT) deficiency is a rare genetic disorder that affects the kidneys and urinary tract. The condition can manifest at any age, from infancy to adulthood. Here are some common signs and symptoms associated with APRT deficiency:

• Kidney Stones: Recurrent kidney stones are the most common feature of this condition [10][15].
• Urinary Tract Stones: Urinary tract stones are also a frequent symptom, which can cause pain during urination and difficulty releasing urine [10][15].
• Nephrolithiasis: Kidney stones can create blockages in the urinary tract, leading to nephrolithiasis (kidney stone formation) [9].
• Urolithiasis: Urinary tract stones can also cause urolithiasis (urinary tract stone formation) [8].
• Crystalline Nephropathy: The excessive production and renal excretion of 2,8-dihydroxyadenine (DHA) can lead to crystalline nephropathy, causing acute kidney injury episodes and progressive chronic kidney disease (CKD) [11][13].
• Hematuria: Blood in the urine (hematuria) is another symptom associated with APRT deficiency [9].
• Acute Kidney Injury: Episodes of acute kidney injury can occur due to DHA crystal nephropathy [11][13].
• Chronic Kidney Disease: Progressive chronic kidney disease (CKD) can develop over time, leading to permanent damage and potentially kidney failure [5].

Age-Related Symptoms

Symptoms of APRT deficiency may start to appear at various ages, from infancy to adulthood. In infancy, symptoms may include a reddish-brown stain in the baby's diapers due to passing kidney stones in urine [14]. In childhood and adulthood, symptoms can range from recurrent kidney stones to more severe complications like CKD.

It is essential for individuals with APRT deficiency to seek medical attention promptly if they experience any of these symptoms. Early diagnosis and treatment can help manage the condition and prevent further complications.

Adenine phosphoribosyltransferase (APRT) deficiency is a genetic disorder that affects the kidneys and urinary tract. Diagnostic tests for APRT deficiency are crucial in confirming the diagnosis.

Diagnostic Tools:

• Stone analysis: The presence of dihydroxyadenine (DHA) crystals or stones in the urine can confirm APRT deficiency [1].
• Crystalluria examination: This test involves examining the urine for DHA crystals, which is a key diagnostic feature of APRT deficiency [2].
• APRT activity measurement: Measuring the activity of APRT enzyme in red blood cells can help confirm the diagnosis [9].

Other Diagnostic Tests:

• Genetic testing: Next-generation sequencing (NGS) tests can be used to identify mutations in the APRT gene, confirming the diagnosis [6].
• Urine analysis: The presence of DHA in urine and kidney stones is often a sign of APRT deficiency [8].

These diagnostic tools are essential in confirming the diagnosis of APRT deficiency. A simple method for diagnosing APRT deficiency using urine has been described, which involves T.l.c. of 1 μl of urine from a child [3].

Treatment Options for Adenine Phosphoribosyltransferase (APRT) Deficiency

Adenine phosphoribosyltransferase (APRT) deficiency is a rare inherited metabolic disorder that can lead to the formation of kidney stones and chronic kidney disease. Fortunately, there are effective treatment options available.

Allopurinol: The Cornerstone of Treatment

The primary treatment for APRT deficiency is allopurinol, a xanthine dehydrogenase (XDH) inhibitor that reduces the production of 2,8-dihydroxyadenine (DHA), the compound responsible for kidney stone formation. Allopurinol therapy has been shown to be effective in preventing new kidney stones from forming and reducing DHA crystalluria [1][4].

Other Treatment Options

In addition to allopurinol, febuxostat is another xanthine oxidase inhibitor that has been found to be effective in reducing urinary DHA excretion in APRT deficiency patients. Febuxostat was shown to be significantly more efficacious than allopurinol in some studies [8].

Prevention of Kidney Disease

Treatment with allopurinol or febuxostat can prevent kidney disease and chronic kidney disease in most patients with APRT deficiency. Regular monitoring and follow-up care are essential to ensure the effectiveness of treatment and prevent complications.

References:

• [1] Bollée G, et al. (2012) - APRT deficiency is a rare inherited metabolic disorder that leads to the formation and hyperexcretion of 2,8-dihydroxyadenine (DHA) into urine.
• [4] Bollée G, et al. (2014) - Allopurinol is the cornerstone of treatment for APRT deficiency. Allopurinol therapy usually leads to a rapid reduction of DHA crystalluria and stone formation.
• [8] Balasubramaniam GS, et al. (2016) - Adenine phosphoribosyltransferase deficiency is an inborn error of metabolism that can cause kidney disease from crystalline nephropathy or kidney stones.
• [3] Li J, et al. (2019) - Reducing DHA production by xanthine oxidase inhibition is the cornerstone of pharmacological therapy for APRT deficiency. Allopurinol is the most used drug in this treatment.
• [5] - Treatment of adenine phosphoribosyltransferase deficiency includes allopurinol and can prevent kidney stones and chronic kidney disease in most patients.
• [6] - How is APRT-D treated? APRT-D can be treated with a medicine called allopurinol, which blocks the production of DHA, preventing new kidney stones being formed.

The differential diagnosis for adenine phosphoribosyltransferase (APRT) deficiency includes other known causes of radiolucent kidney stones such as uric acid nephrolithiasis, Xanthinuria, and Primary hyperoxaluria [1][3]. These conditions can present with similar symptoms to APRT deficiency, making accurate diagnosis challenging.

Some key points to consider in the differential diagnosis of APRT deficiency are:

• Uric acid nephrolithiasis: This condition is characterized by the formation of uric acid stones in the kidneys, which can be radiolucent like those seen in APRT deficiency [1].
• Xanthinuria: This is a rare genetic disorder that affects the metabolism of xanthine and hypoxanthine, leading to the formation of xanthine stones in the kidneys [3].
• Primary hyperoxaluria: This is a rare inherited disorder that affects the metabolism of oxalate, leading to the formation of oxalate stones in the kidneys [1].

It's worth noting that APRT deficiency can be distinguished from these conditions through specific diagnostic tests, such as stone analysis or examination of crystals in urine for the demonstration of DHA [4][8].