Year : 2010 | Volume
: 21 | Issue : 2 | Page : 328--331
Tahar Gargah1, Afif Essid2, Aymen Labassi1, Mourad Hamzaoui2, Mohamed Rachid Lakhoua1,
1 Department of Pediatrics, Charles Nicolle Hospital, Bab Saadoun, Tunisia
2 Department of Pediatric Surgery, University Children's Hospital, Bab Saadoun, Tunisia
Department of Pediatrics, Charles Nicolle Hospital, Tunis
Hereditary xanthinuria type I, a defect of purine matabolism, results from a genetic deficiency of xanthine oxidase. It is an uncommon cause of stone formation in children. We report here two children with xanthine urolithiasis. The first patient was an 8-year-old boy who presented with repeated episodes of hematuria evaluated with excretory urography, which demonstrated radiolucent pelvic stone in the right kidney, causing hydronephrosis. He had pyelolithotomy, and the extracted stone consisted of pure xanthine. Family study revealed an asymptomatic xanthinuria in younger brother. The second patient was a 5-year-old boy who had a 2-week history of abdominal pain and gross hematuria. Conventional excretory intravenous urography showed a non-functioning right kidney. Nephrectomy was performed, and histology revealed end-stage pyelonephritis. The calculi consisted of pure xanthine. In both patients, plasma and urinary concentrations of uric acid were low but xanthine and hypoxanthine concentrations were markedly elevated. Xanthine urolithiasis is usually a benign condition, easy to prevent or cure by appropriate alkalinization, forced hydration and restriction of dietary purines. However asymptomatic, and therefore undiagnosed, stones may invade the kidney and urinary tract, resulting in destruction of parenchyma, nephrectomy and renal failure.
|How to cite this article:|
Gargah T, Essid A, Labassi A, Hamzaoui M, Lakhoua MR. Xanthine urolithiasis.Saudi J Kidney Dis Transpl 2010;21:328-331
|How to cite this URL:|
Gargah T, Essid A, Labassi A, Hamzaoui M, Lakhoua MR. Xanthine urolithiasis. Saudi J Kidney Dis Transpl [serial online] 2010 [cited 2020 Dec 2 ];21:328-331
Available from: https://www.sjkdt.org/text.asp?2010/21/2/328/60205
Xanthinuria type I, a rare hereditary disorder, is characterized by a marked and isolated deficiency of xanthine oxidase activity in the tissues, resulting in hypouricemia and hypouricosuria.  Total urinary purine excretion is not increased, whereas excretion of xanthine and hypoxanthine is considerably increased as a response to the elevated serum levels of these oxypurines.  Clinical symptoms may include crystalluric urolithiasis and acute renal failure. When unrecognized, xanthinuria can lead to nephrectomy or end-stage renal failure. , The following cases illustrate the interest of earlier recognition to prevent stone formation and to avoid nephrectomy.
An 8-year-old boy was referred to our center for evaluation of urolithiasis. He was born at term from apparently healthy consanguineous parents (first cousins), and he had no familial history of renal stone disease. His psychomotor development and physical growth were normal. The patient presented with a 2-year history of intermittent left flank associated with macroscopic hematuria explored by ultrasonography at 7 years of age, which was reported as normal. He suffered from repeated episodes of hematuria 12 months later, evaluated with excretory urography, which demonstrated radiolucent pelvic stone in the right kidney, causing distension of the intra-renal collecting system. The patient underwent pyelolithotomy and was referred to our department for further investigation of his renal stone disease.
Stone analysis demonstrated 100% xanthine composition. Serum concentration and urinary excretion of xanthine and hypoxanthine were massively increased. Screening for metabolic disorders detected markedly decreased uric acid concentrations in the urine and plasma. Other biochemical tests included serum creatinine, calcium, phosphorus, alkaline phosphatase and bicarbonate, and all were within normal limits. Urinary calcium/creatinine ratio was normal in a 24-hour urine specimen. Urinary citrate and oxalate excretion was normal. Accordingly, we diagnosed the patient to have hereditary xanthinuria.
An increase in fluid intake as supplement free water and a low-purine diet were recommendded. Oral sodium bicarbonate therapy was initiated, and the dose was adjusted to maintain the urine pH at 7. The repeated ultrasound examination revealed no recurrence of stones. At his present age of 15 years, the patient remains free of nephrolithiasis.
Serum uric acid levels in the patient's mother and father were normal. His younger brother, with age of 4 years, showed a significant hypouricosuria and hypo-uricemia without nephrolithiasis or nephrocalcinosis on an ultrasound examination, and his creatinine clearance was normal. Oral sodium bicarbonate, high fluid intake and low-purine diet were initiated too. No renal stone was detected later with the yearly ultrasound examination.
A 5-year-old boy was admitted to another local hospital mainly for renal colic and gross hematuria. The parents, who were first cousins, denied having health problems or familial history of renal stone. Two weeks before hospitalization, the patient had abdominal pain and vomited frequently, and later presented with gross hematuria. A plain abdominal radiography showed the absence of radiopaque stones, and he was treated at the local hospital with intravenous antispasmotic.
Ten days later, the patient was transferred to our hospital for further evaluation of his repeated episodes of gross hematuria and renal colic. Physical examination on arrival, revealed a healthy appearing child. Mental and motor development was appropriate for age. We confirmed the presence of macroscopic hematuria with no hypertension or renal failure. Ultrasonography evaluation of the urinary tract revealed the presence of multiple calculi in the right kidney with moderate distention of the left pyelocalyceal system. An excretory urogram demonstrated a well-functioning left kidney and a nonfunctioning right kidney [Figure 1]. All the findings were also documented by Tc-99m diethylenetriamine pentaacetic acid and Tc-99m dimercaptosuccinic acidscintigraphy. At operation, many calculi were impacted in the right kidney with dilatation of the pylocalyceal system. Nephrectomy was performed, and the histologic examination revealed end-stage chronic pyelonephritis [Figure 2]. The examination of the extracted stones with infrared spectrophotometry revealed pure xanthine content. The serum uric acid level was particulary low at 22 µmol/L. After right nephrectomy, the renal function remained normal. The patient was treated with oral sodium bicarbonate to maintain his urinary pH at 7 and was encouraged to drink more fluids. He had no stone in the left kidney during the next 40 months of follow-up.
The defect of this xanthine oxidase is uncommon causes of pediatric stone formation.  During the last decade, in the pediatric nephrology department of Charles Nicolle hospital in Tunisia, we noted that less than 3% of the enfants referred for renal stone had xanthinuria. Arikyants  and Sarkissian  reported a low frequency of xanthine stone around 0.1%, but Al-Aissa  found a very high proportion about 13%.
A minority of patients with hereditary xanthinuria have renal calculi or nephrocalcinosis during childhood. More than 50% of all children do not develop calculi.  The younger brother of the first patient was asymptomatic and did not have calculi. Xanthinuric children who have stones during childhood excrete higher amounts of xanthine and consume few fluids than those who do not. The low urinary citrate excretion noted in the first patient may be another important factor of stone formation in xanthinuria.
The severity of the nephrolithiasis resulting in kidney destruction and nephrectomy is uncommon in children.  It may be explained by late diagnosis, recurrent urinary tract infection, and staghorn urolithiasis. The progression of renal disease resulting in dialysis, transplantation, and even death has been observed. 
Many symptoms have been reported in xanthinuria such as hematuria, urinary tract infection, and renal colic cristalluria. Moreover, exerciseinduced acute renal failure was described in both adults and children. , However, most cases of xanthinuria have been discovered accidentally in patients being investigated for other disorders. 
The plasma uric acid in xanthinuria type I is very low and even undetectable and is replaced by xanthine and hypoxanthine. In fact, there is complete absence of uric acid in body fluids and its replacement predominantly by xanthine.  Confirmation of the enzyme defect is rarely made because it needs invasive techniques such as intestinal or liver biopsy.  Differential diagnosis for xanthinuria type I includes mainly xanthinuria type II with combined xanthine dehydrogenase and aldehyde oxidase deficiency. Both types of defects are clinically similar, but can be distinguished by urinary screening. 
The management of xanthinuria type I includes high fluid intake and a low-purine diet. Alkalinization of the urine elevates modestly the solubility of xanthine. Increased citrate excretion induced by oral potassium citrate administration prevents the stone formation.  The treatment modality of xanthine stones depends on their size and location. Surgical stone removal should be reserved for urinary obstruction when lithotripsy has failed to relieve it. 
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