Cystinuria in Childhood

We report a 2-year-old boy, presenting a 1-day history of difficulty in urinating and abdominal pain. He did not have fever or vomiting. He was born at full-term gestation after an uncomplicated pregnancy with a birth weight of 3500 gr. from a consanguineous family (first degree cousins). His prenatal and natal history was uneventful. His family history was unremarkable. His family history showed negativity for nephrolithiasis as well as chronic kidney disease. Physical examination revealed mild suprapubic tenderness. Laboratory examinations including acute phase reactants, serum electrolytes and renal function tests were normal. Urinary examination showed remarkable hematuria and leukocyturia with 100 cells per high power field while the urinary culture was sterile. Direct abdominal radiography showed multiple stones in the bladder and also in the renal pelvis in the right kidney ([Fig. 1-A], arrows). Urinary ultrasonography was performed to confirm the diagnosis and to evaluate any possible complications. It revealed multiple bladder stones reaching 2 cm in length. The right renal pelvis included a non-obstructive stone approximately 1 cm in diameter. Further assessment of urine for etiology included screening with the cyanide-nitroprusside test. A positive result was obtained ([Fig. 1-C], arrow). Further identification and quantification of cystine might be accomplished by thin-layer chromatography ([Fig. 1-D], arrow). However, the confirmation for the quantitative analysis was determined with high-performance liquid chromatography for urine amino acids. Diagnostically, urinary levels of dibasic amino acids L-lysine, L-arginine, and L-ornithine, and most prominently of cystine were elevated more than five times the upper range ([Fig. 1-E], arrow; [Fig. 1-F]; red frame). The results were as follows; for L-lysine: 588.1 mmol/molcrea (normal range: 10–46 mmol/molcrea); L-arginine: 1304 mmol/molcrea ( normal range: 0–9 mmol/molcrea); L-ornithine: 16,76 mmol/molcrea (normal range: 0–7 mmol/molcrea) and cysteine: 669,8 mmol/molcrea ( normal range: 4–15 mmol/molcrea). A diagnosis of cystinuria was made. First-line therapy included increased fluid intake, urinary alkalinization with potassium citrate, and a low sodium diet. The volume of fluid intake as water was adjusted to the weight of the patient and the target amount was 70–100 ml/kg/day. Nighttime fluid intake was recommended for the patient to reach the target volume. D-penicillamine was used for chelation therapy for six months. In cases where significant cystinuria persists despite medical treatment, a number of therapies have been proposed. Thus shock-wave lithotripsy was found to be less effective in cystine stones; more invasive procedures like percutaneous nephrolithotomy (PCL) were needed especially for larger stones. The stones were removed by PCL without complications ([Fig. 1-B]). The patient was continued on captopril which is a second-generation chelating agent with first-line therapy by lowering the urine cystine levels. Urinary ultrasonography was used for post-operative follow-up. Informed consent was obtained from the parents for the publication of the case.

Fig. 1 A: Direct abdominal radiography showed multiple stones in the bladder and also in the renal pelvis in the right kidney (arrows). B: Cystine stones removed by percutaneous nephrolithotomy. C: Positive cyanide-nitroprusside test in the urine. D: Thin-layer chromatography showing cystine dots (arrow). E, F: High-performance liquid chromatography results for urine amino acids showing elevation of cystine in the urine (arrow; red frame).

Publication History

Article published online:
20 July 2021