OBJECTIVE: To review the history, basic defect, pathogenesis, clinical manifestations, diagnosis, and treatment of nephropathic cystinosis. DESIGN: Lysosomal membrane transport studies, clinical reports, and a historically controlled 7-year trial of oral cysteamine therapy. SETTING: University centers in the United States and Canada. PATIENTS: One hundred forty-eight children, aged 0 to 12, with nephropathic cystinosis before renal transplant, who had renal tubular Fanconi syndrome, failure to grow, corneal cystine crystals, and elevated leukocyte cystine; 34 patients, aged 9 to 29, after transplant, some with visual impairment, corneal erosions, pancreatic dysfunction, or neurologic deterioration. INTERVENTION: Before transplant, replacement of renal losses, and treatment with oral cysteamine (55 mg/kg body weight.d for 1 to 6 years) and topical cysteamine eyedrops (0.1%, 1 drop/h while awake, for 6 months). After transplant, oral cysteamine and symptomatic treatment of late complications. MEASUREMENTS AND MAIN RESULTS: Untreated patients reached renal failure at age 10. Oral cysteamine lowered leukocyte cystine over 80%, and in patients before transplant, improved growth and preserved renal function (mean creatinine clearance [+/- SE], 0.64 +/- 0.04 mL/s.1.73 m2 [38.5 +/- 2.5 mL/min.1.73 m2] in the cysteamine group compared with 0.50 +/- 0.03 mL/s.1.73 m2 [29.7 +/- 2.0 mL/min.1.73 m2] in controls; 95% CI for the difference, 1.8 to 15.8). Cysteamine eyedrops cleared the corneal crystals of two children less than 2 years old. CONCLUSIONS: Cystinosis is a lysosomal storage disease due to impaired transport of cystine out of lysosomes. In young children, growth can be improved and renal deterioration delayed or prevented by oral cysteamine. Nonrenal complications after transplant might be prevented with long-term oral cysteamine.
OBJECTIVE: To review the history, basic defect, pathogenesis, clinical manifestations, diagnosis, and treatment of nephropathic cystinosis. DESIGN: Lysosomal membrane transport studies, clinical reports, and a historically controlled 7-year trial of oral cysteamine therapy. SETTING: University centers in the United States and Canada. PATIENTS: One hundred forty-eight children, aged 0 to 12, with nephropathic cystinosis before renal transplant, who had renal tubular Fanconi syndrome, failure to grow, corneal cystine crystals, and elevated leukocyte cystine; 34 patients, aged 9 to 29, after transplant, some with visual impairment, corneal erosions, pancreatic dysfunction, or neurologic deterioration. INTERVENTION: Before transplant, replacement of renal losses, and treatment with oral cysteamine (55 mg/kg body weight.d for 1 to 6 years) and topical cysteamine eyedrops (0.1%, 1 drop/h while awake, for 6 months). After transplant, oral cysteamine and symptomatic treatment of late complications. MEASUREMENTS AND MAIN RESULTS: Untreated patients reached renal failure at age 10. Oral cysteamine lowered leukocyte cystine over 80%, and in patients before transplant, improved growth and preserved renal function (mean creatinine clearance [+/- SE], 0.64 +/- 0.04 mL/s.1.73 m2 [38.5 +/- 2.5 mL/min.1.73 m2] in the cysteamine group compared with 0.50 +/- 0.03 mL/s.1.73 m2 [29.7 +/- 2.0 mL/min.1.73 m2] in controls; 95% CI for the difference, 1.8 to 15.8). Cysteamine eyedrops cleared the corneal crystals of two children less than 2 years old. CONCLUSIONS:Cystinosis is a lysosomal storage disease due to impaired transport of cystine out of lysosomes. In young children, growth can be improved and renal deterioration delayed or prevented by oral cysteamine. Nonrenal complications after transplant might be prevented with long-term oral cysteamine.