Nephropathic Cystinosis in Adults: Natural History and Effects of Oral Cysteamine Therapy

Nephropathic Cystinosis in Adults: Natural History and Effects of Oral Cysteamine Therapy

William A. Gahl, MD, PhD;
Joan Z. Balog, RN, MSN; and
Robert Kleta, MD, PhD

From the National Human Genome Research Institute and Intramural Office of Rare Diseases, National Institutes of Health, Bethesda, Maryland.

Abstract

Background: The full burden of nephropathic cystinosis in adulthood and the effects of long-term oral cysteamine therapy on its nonrenal complications have not been elucidated.

Objective: To assess the severity of cystinosis in adults receiving and not receiving oral cysteamine therapy.

Design: Case series.

Setting: National Institutes of Health Clinical Center.

Patients: 100 persons (58 men and 42 women) age 18 to 45 years with nephropathic cystinosis examined between January 1985 and May 2006.

Measurements: Historical data were collected on renal transplantation, administration of oral cysteamine, and time and cause of death. Patients were evaluated for height and weight; thyroid, pulmonary, and swallowing function; muscle atrophy; hypogonadism (in men); retinopathy; vascular and cerebral calcifications; diabetes mellitus; and homozygosity for the common 57-kb deletion in CTNS. Laboratory studies were also performed.

Results: Of 100 adults with nephropathic cystinosis, 92 had received a renal allograft and 33 had died. At least half of the patients had hypothyroidism, hypergonadotropic hypogonadism (in men), pulmonary insufficiency, swallowing abnormalities, or myopathy. One third of the patients had retinopathy or vascular calcifications, and 24% had diabetes. Homozygosity for the 57-kb CTNS deletion was associated with an increased risk for death and morbidity. The 39 patients who received long-term (≥8 years) oral cysteamine therapy were taller and heavier, had a renal allograft later in life, had lower cholesterol levels, and experienced fewer complications and deaths than patients who received cysteamine for fewer than 8 years. The frequency of diabetes mellitus, myopathy, pulmonary dysfunction, hypothyroidism, and death increased as time off cysteamine treatment increased, and it decreased as time on cysteamine therapy increased.

Limitations: The study was retrospective and not randomized. The criteria used to measure adequacy of treatment were arbitrary.

Conclusions: Untreated nephropathic cystinosis causes extensive morbidity and death in adulthood. Long-term oral cysteamine therapy mitigates these effects.

Article and Author Information

Acknowledgments: The authors thank Isa Bernardini, MEd, for performing the leukocyte cystine assays; Kevin O'Brien, NP, for collection of patient data; and Brad Tinloy, BS, for statistical consultation.
Grant Support: By the Intramural Research Programs of the National Human Genome Research Institute and the National Institute of Child Health and Human Development, National Institutes of Health.
Potential Financial Conflicts of Interest: None disclosed.
Requests for Single Reprints: William A. Gahl, MD, PhD, National Human Genome Research Institute, National Institutes of Health, 10 Center Drive, Building 10, Room 10C-103, Bethesda, MD 20892-1851; e-mail, bgahl{at}helix.nih.gov.
Current Author Addresses: Dr. Gahl and Ms. Balog: National Human Genome Research Institute, National Institutes of Health, 10 Center Drive, Building 10, Room 10C-103, Bethesda, MD 20892-1851.
Dr. Kleta: University College London, Royal Free Hospital, Roland Hill Street, Hampstead, London NW3 2PF, United Kingdom.
Author Contributions: Conception and design: W.A. Gahl.
Analysis and interpretation of the data: W.A. Gahl, J.Z. Balog, R. Kleta.
Drafting of the article: W.A. Gahl, J.Z. Balog, R. Kleta.
Critical revision of the article for important intellectual content: W.A. Gahl, R. Kleta.
Final approval of the article: W.A. Gahl, J.Z. Balog, R. Kleta.
Provision of study materials or patients: W.A. Gahl, R. Kleta.
Statistical expertise: W.A. Gahl.
Obtaining of funding: W.A. Gahl.
Administrative, technical, or logistic support: W.A. Gahl, J.Z. Balog.
Collection and assembly of data: W.A. Gahl, J.Z. Balog.