Cystinosis: Progress in a Prototypic Disease
- William A. Gahl, MD, PhD;
- Jess G. Thoene, MD;
- Jerry A. Schneider, MD;
- Sean O'Regan, MD;
- Muriel I. Kaiser-Kupfer, MD; and
- Toichiro Kuwabara, MD
Abstract
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.
Article and Author Information
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An edited summary of a Clinical Staff Conference held 4 November 1987 at the Amphitheater, Building 10, Bethesda, Maryland, sponsored by the National Institutes of Health, U.S. Department of Health and Human Services.
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Authors who wish to cite a section of the conference and specifically indicate its author can use this example for the form of reference:
Thoene JG. Clinical characteristics and recent progress in nephropathic cystinosis, pp 557-559. In: Gahl WA, moderator. Cystinosis: progress in a prototypic disease. Ann Intern Med. 1988;109:557-569.
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Grant Support: Dr. Schneider was supported by grant DK 18434, General Clinical Research Center grant RR00827, and contract NOI-HD-62927 from the National Institutes of Health and by gifts from the Bernard L. Maas Foundation and the Cystinosis Foundation. Dr. Thoene was supported by grants DK 25548 and 5-MOI-RR-00042 to the University of Michigan. Support from the Generic Pharmaceutical Industry Association Institute for Orphan Drugs and the Pharmaceutical Manufacturers Association is also gratefully acknowledged.
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Requests for Reprints: William A. Gahl, MD, PhD, NICHD, National Institutes of Health, Building 10, Room 8C-429, Bethesda, MD 20892.
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Current Author Addresses: Dr. Gahl: NICHD, National Institutes of Health, Building 10, Room 8C-429, Bethesda, MD 20892.
Dr. Thoene: Department of Pediatrics, 2612 School of Public Health I, 109 Observatory, University of Michigan Medical School, Ann Arbor, MI 48109.
Dr. Schneider: Department of Pediatrics, M009F, University of California-San Diego, La Jolla, CA 92037.
Dr. O'Regan: Nephrology Service, Hôpital Ste. Justine, 3175 Côte Sainte-Catherine, Montreal, Quebec H3T 1C5.
Dr. Kaiser-Kupfer: National Eye Institute, National Institutes of Health, Building 10, Room 10N224, Bethesda, MD 20892.
Dr. Kuwabara: National Eye Institute, National Institutes of Health, Building 10, Room 10N115, Bethesda, MD 20892.
- © 1988 American College of Physicians
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