Parenchymal organ cystine depletion with long-term cysteamine therapy.
Nephropathic cystinosis is a lysosomal storage disorder characterized by renal failure, multisystem organ damage, and poor growth. Oral cysteamine therapy retards renal deterioration and enhances growth, but parenchymal organ cystine depletion has never been documented. We measured skeletal muscle cystine in 11 cystinosis patients not treated with cysteamine; analysis of their values plus 11 published values showed that muscle cystine increases linearly with age in cystinosis patients (slope, 0.074 nmol half-cystine/mg wet wt/year). In contrast, 15 patients treated for 4 to 11 years with oral cysteamine had a relatively constant muscle cystine content (slope, 0.004 nmol half-cystine/mg wet wt/year). The treated patients' mean muscle cystine, 0.091 +/- 0.064 (SD) nmol half-cystine/mg wet wt, was significantly less (P < 0.001) than that for the 11 youngest untreated patients, 0.754 +/- 0.534 nmol half-cystine/mg wet wt. On postmortem examination, a 9-year-old cystinosis patient treated for 8 years with oral cysteamine had liver, kidney, pancreas, lung, and spleen cystine values 5 to 90 times lower than those of an untreated age-matched control. We conclude that long-term oral cysteamine therapy routinely depletes cystinotic skeletal muscle of cystine; cysteamine is the treatment of choice for the prevention of both renal and nonrenal complications of cystinosis.
Gahl
W A
WA
Section on Human Biochemical Genetics, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892.
Charnas
L
L
Markello
T C
TC
Bernardini
I
I
Ishak
K G
KG
Dalakas
M C
MC
D000293:Adolescent; D002648:Child; D003543:Cysteamine / Q000627:therapeutic use*; D003553:Cystine / Q000378:metabolism*; D003554:Cystinosis / Q000188:drug therapy* / Q000378:metabolism*; D005198:Fanconi Syndrome / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D006801:Humans; D007223:Infant; D007668:Kidney / Q000378:metabolism; D007674:Kidney Diseases / Q000188:drug therapy* / Q000378:metabolism*; D008099:Liver / Q000378:metabolism / Q000473:pathology; D008168:Lung / Q000378:metabolism; D008297:Male; D008855:Microscopy, Electron, Scanning; D009132:Muscles / Q000378:metabolism; D010179:Pancreas / Q000378:metabolism; D013154:Spleen / Q000378:metabolism
D003553:Cystine; D003543:Cysteamine