Nephropathic cystinosis in adults: natural history and effects of oral cysteamine therapy.
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.


METHODS
Case series.


METHODS
National Institutes of Health Clinical Center.


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


METHODS
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 (> or =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.


CONCLUSIONS
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.
Gahl
William A
WA
National Human Genome Research Institute and Intramural Office of Rare Diseases, National Institutes of Health, Bethesda, Maryland 20892-1851, USA. bgahl@helix.nih.gov
Balog
Joan Z
JZ
Kleta
Robert
R
D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D026921:Amino Acid Transport Systems, Neutral / Q000235:genetics; D003543:Cysteamine / Q000627:therapeutic use*; D003554:Cystinosis / Q000150:complications* / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D005198:Fanconi Syndrome / Q000209:etiology* / Q000601:surgery; D005260:Female; D017353:Gene Deletion; D006801:Humans; D016030:Kidney Transplantation; D007684:Kidney Tubules / Q000473:pathology; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies
D026921:Amino Acid Transport Systems, Neutral; C111445:CTNS protein, human; D003543:Cysteamine