Penicillamine therapy for pediatric cystinuria: experience from a cohort of American children

PURPOSE: Cystinuria, an inherited defect of dibasic amino acid transport, causes accumulation of urinary cystine and cystine urolithiasis. In adults penicillamine reduces stone formation but has a high incidence of dose limiting toxicity. We evaluated the effects of penicillamine in preventing stone formation and with respect to toxicity in our cystinuria cohort at a pediatric biochemical genetics clinic. MATERIALS AND METHODS: We reviewed the charts of all 11 children with cystinuria treated at our clinic using a gradual dose escalation of penicillamine. Mean +/- SD patient age at diagnosis was 5.8 +/- 4.3 years (range 1.2 to 12). We tracked urinary cystine concentration before and after initiation of treatment, penicillamine side effects and incidence of new stones during maintenance therapy. RESULTS: During the gradual escalation of penicillamine to the target dose none of the 11 patients experienced toxicity and all had improved urinary cystine concentration (mean +/- SD percent reduction 54% +/- 25%, range 5% to 81%). We followed the patients for a total of 1,203 months (mean +/- SD 109 +/- 73 months, range 41 to 221), periodically assessing urinary cystine concentration, urine protein content, complete blood count, blood urea nitrogen, creatinine and liver function. During this time only 2 patients experienced significant side effects and no patient had stones or stone crises while compliant with treatment. CONCLUSIONS: In our cohort penicillamine was well tolerated after gradual initiation and it reduced urinary cystine concentration. Long-term compliance with the medication appeared to protect patients from acute stone crises.