Hereditary xanthinuria - Clinicals, Diagnosis, and Management

Endocrinology, Metabolism and Nutrition

Clinicals - History

Fact Explanation
Loin to groin pain Xanthinuria is excess urinary excretion of the xanthine which is a hereditary condition. This is due to the genetic deficiency of enzyme, xanthine dehydrogenase that is responsible for degrading hypoxanthine and xanthine to uric acid leaving excess hypoxanthine and xanthine amounts. Out of these two, hypoxanthine can be metabolized using hypoxanthine guanine phosphoribosyltransferase where xanthine is accumulated in plasma. Xanthine can form crystals in the tubules, later parenchymal deposits and calculi formation. Unlike the other stones, these are radiolucent stones. Sometimes they might experience the passage of multiple brownish yellow stones with urine. Loin to groin pain
Xanthinuria is excess urinary excretion of the xanthine which is a hereditary condition. This is due to the genetic deficiency of enzyme, xanthine dehydrogenase that is responsible for degrading hypoxanthine and xanthine to uric acid leaving excess hypoxanthine and xanthine amounts. Out of these two, hypoxanthine can be metabolized using hypoxanthine guanine phosphoribosyltransferase where xanthine is accumulated in plasma. Xanthine can form crystals in the tubules, later parenchymal deposits and calculi formation. Unlike the other stones, these are radiolucent stones. Sometimes they might experience the passage of multiple brownish yellow stones with urine.
Nausea and vomiting May accompany the ureteric colic. Nausea and vomiting
May accompany the ureteric colic.
Dysuria, urinary frequency, urine incontinence They may experience pain while passing urine, increased frequency of micturition due to the calculi formation. These can also be due to the urinary tract infection. Dysuria, urinary frequency, urine incontinence
They may experience pain while passing urine, increased frequency of micturition due to the calculi formation. These can also be due to the urinary tract infection.
Haematuria Calculi can damage the tubules and parenchyma and may cause haematuria. Haematuria
Calculi can damage the tubules and parenchyma and may cause haematuria.
Reduced urine output Stones can invade the kidney and urinary tract, causing destruction of parenchyma, therefore acute and chronic renal failure are complications of xanthinuria. If there is bilateral obstruction due to the calculi they will presenting with acute renal failure of sudden onset. Reduced urine output
Stones can invade the kidney and urinary tract, causing destruction of parenchyma, therefore acute and chronic renal failure are complications of xanthinuria. If there is bilateral obstruction due to the calculi they will presenting with acute renal failure of sudden onset.
Muscle cramps, muscle pain, muscle stiffness Accumulation of xanthine inside the muscles can cause muscle pathology-"myopathy". This might be aggravated after exercise. Muscle cramps, muscle pain, muscle stiffness
Accumulation of xanthine inside the muscles can cause muscle pathology-"myopathy". This might be aggravated after exercise.
Joint pain and swelling Accumulation of xanthine in the joints over a long period of time may result in joint problems. This is a rare manifestation of the disease. Joint pain and swelling
Accumulation of xanthine in the joints over a long period of time may result in joint problems. This is a rare manifestation of the disease.
History of volume depletion: Fasting, blood loss, reduced iurine output Xanthine is well cleared from the kidney therefore if there is volume reduction, it favours the calculi formation. History of volume depletion: Fasting, blood loss, reduced iurine output
Xanthine is well cleared from the kidney therefore if there is volume reduction, it favours the calculi formation.
Age of presentation Commonly presents in the paediatric age group. Young children may present with nonspecific symptoms such as crying, vomiting, poor feeding and failure to thrive. Age of presentation
Commonly presents in the paediatric age group. Young children may present with nonspecific symptoms such as crying, vomiting, poor feeding and failure to thrive.
Family history of renal and ureteric stones This is hereditary condition with a genetic basis. Family history of renal and ureteric stones
This is hereditary condition with a genetic basis.

Clinicals - Examination

Fact Explanation
Febrile Due to the superadded urinary tract infections. Febrile
Due to the superadded urinary tract infections.
Flank tenderness They might have tenderness on palpation due to the calculus disease. Flank tenderness
They might have tenderness on palpation due to the calculus disease.
Speech problems, delayed psychomotor development and behavioural problems Mental delay and autistic disorders are associated with xanthinuria in some children. . Speech problems, delayed psychomotor development and behavioural problems
Mental delay and autistic disorders are associated with xanthinuria in some children. .

Investigations - Diagnosis

Fact Explanation
Urinalysis This can reveal xanthine crystals, red blood cells and pus cells. They can have microscopic haematuria even in the absence of macroscopic haematuria. Urinalysis
This can reveal xanthine crystals, red blood cells and pus cells. They can have microscopic haematuria even in the absence of macroscopic haematuria.
24-hour urine collection of urine for calcium, oxalate, uric acid Uric acid levels are low or undetectable in the hereditary xanthinuria. Xanthine and hypoxanthine excretion in the urine may be elevated. 24-hour urine collection of urine for calcium, oxalate, uric acid
Uric acid levels are low or undetectable in the hereditary xanthinuria. Xanthine and hypoxanthine excretion in the urine may be elevated.
Fractional excretion of uric acid Fractional excretion of uric acid is reduced. Fractional excretion of uric acid
Fractional excretion of uric acid is reduced.
Xanthine and hypoxanthine levels Serum levels are markedly increased in these patients. Xanthine and hypoxanthine levels
Serum levels are markedly increased in these patients.
X-ray and ultrasoundscan Kidney, ureters, and bladder (KUB) Assessment and management of of calculus disease requires these investigations. Xanthine stones appear as radiolucent stones on radiography. Ultrasound can demonstrate both the function and structure of the kidney and any hydronephrosis with dilatation of the pelvicalyceal system. X-ray and ultrasoundscan Kidney, ureters, and bladder (KUB)
Assessment and management of of calculus disease requires these investigations. Xanthine stones appear as radiolucent stones on radiography. Ultrasound can demonstrate both the function and structure of the kidney and any hydronephrosis with dilatation of the pelvicalyceal system.
Intravenous pyelography Will demonstrate filling defect due to the calculus in pelvis or the ureters. Intravenous pyelography
Will demonstrate filling defect due to the calculus in pelvis or the ureters.
Analysis of renal stones using an X-ray diffractometer Renal stones can be analysed using an X-ray diffractometer which will demonstrate the xanthine. Analysis of renal stones using an X-ray diffractometer
Renal stones can be analysed using an X-ray diffractometer which will demonstrate the xanthine.

Investigations - Management

Fact Explanation
X-ray and ultrasound scan kidney ureter bladder Important to assess the recurrence of the calculus disease. X-ray and ultrasound scan kidney ureter bladder
Important to assess the recurrence of the calculus disease.
Urine uric acid level Should be increased with the improvement. Urine uric acid level
Should be increased with the improvement.
Serum creatinine, serum electrolytes and blood urea Stones can invade the kidney and urinary tract, causing destruction of parenchyma, therefore acute and chronic renal failure are complications of xanthinuria. Therefore assessment of the renal function is important. Serum creatinine, serum electrolytes and blood urea
Stones can invade the kidney and urinary tract, causing destruction of parenchyma, therefore acute and chronic renal failure are complications of xanthinuria. Therefore assessment of the renal function is important.
Urine culture It is important to see the presence of any infection as it can cause damage to the kidney especially in the presence of an infection. Urine culture
It is important to see the presence of any infection as it can cause damage to the kidney especially in the presence of an infection.
Serum electrolytes, calcium, magnesium, phosphorus, and uric acid levels Important in evaluating the calculus disease. Serum electrolytes, calcium, magnesium, phosphorus, and uric acid levels
Important in evaluating the calculus disease.
Serum creatinine, blood urea Assessment of renal function is important as they can develop acute and chronic renal failure as a complication. Serum creatinine, blood urea
Assessment of renal function is important as they can develop acute and chronic renal failure as a complication.
Serum uric acid levels in the patient's family Serum uric acid levels in the patient's family should be checked and most of the time this reveals asymptomatic xanthinuria. Serum uric acid levels in the patient's family
Serum uric acid levels in the patient's family should be checked and most of the time this reveals asymptomatic xanthinuria.
Allopurinol loading test Xanthinuria is divided into 2 main types as type 1 and 2, by the allopurinol loading test. This test checks the 2 enzymes: xanthine dehydrogenase and aldehyde oxidase. In type I disease there is lack of xanthine dehydrogenase activity with intact aldehyde oxidase activity. In type 2 disease both the enzymes are lacking. Allopurinol loading test
Xanthinuria is divided into 2 main types as type 1 and 2, by the allopurinol loading test. This test checks the 2 enzymes: xanthine dehydrogenase and aldehyde oxidase. In type I disease there is lack of xanthine dehydrogenase activity with intact aldehyde oxidase activity. In type 2 disease both the enzymes are lacking.

Management - Supportive

Fact Explanation
High fluid intake Dehydration and concentrated urine favours the formation of stones, therefore it is necessary to maintain a daily good input. High fluid intake
Dehydration and concentrated urine favours the formation of stones, therefore it is necessary to maintain a daily good input.
Restrict the high purine containing food The foods that contain higher amounts of Purines are rich in beef, pork, poultry, seafood, liver, kidney, peas, beans, spinach, and lentils. Restrict the high purine containing food
The foods that contain higher amounts of Purines are rich in beef, pork, poultry, seafood, liver, kidney, peas, beans, spinach, and lentils.
Caution with certain drugs Xanthine dehydrogenase enzyme is important for the degradation of azathioprine or 6-mercaptopurine. Aldehyde oxidase whose deficiency can be sometimes accompanied with xanthine oxidase deficiency , important for the metabolism of allopurinol , cyclophosphamide, methotrexate, and quinine. Therefore these drugs can reach toxic levels in the presence of xanthine oxidase deficiency. Caution with certain drugs
Xanthine dehydrogenase enzyme is important for the degradation of azathioprine or 6-mercaptopurine. Aldehyde oxidase whose deficiency can be sometimes accompanied with xanthine oxidase deficiency , important for the metabolism of allopurinol , cyclophosphamide, methotrexate, and quinine. Therefore these drugs can reach toxic levels in the presence of xanthine oxidase deficiency.

Management - Specific

Fact Explanation
Treatment of calculi Medical management with follow up or surgical care may be needed in calculus disease. Extracorporeal shock wave lithotripsy and pyelolithotomy are some of the methods used to treat the stones., Treatment of calculi
Medical management with follow up or surgical care may be needed in calculus disease. Extracorporeal shock wave lithotripsy and pyelolithotomy are some of the methods used to treat the stones.,
Sodium bicarbonate Oral sodium bicarbonate therapy is used to make the urine alkaline, increase the solu­bility of xanthine and maintain the urine pH at 7. Sodium bicarbonate
Oral sodium bicarbonate therapy is used to make the urine alkaline, increase the solu­bility of xanthine and maintain the urine pH at 7.
Management of complications Renal disease may require dialysis and transplantation. Management of complications
Renal disease may require dialysis and transplantation.

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