Cystinosis

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Abstract
Cystinosis, a recessively inherited disease characterized by the accumulation of cystine crystals in the cornea, bone marrow and reticuloendothelial cells occurs in 2 distinct forms. In adults it appears to be an entirely benign disorder while in children it is invariably a fatal disease. Clinical features of the childhood variety are related primarily to dysfunction of the renal tubules resulting in the Fanconi syndrome with polyuria, a generalized aminoaciduria, glycosuria, phosphaturia and rickets. A progressive glomerular damage leads to death in uremia usually within the 1st decade of life. A characteristic lesion in the periphery of the retina consisting of a patchy depigmenta-tion is found consistently in the child but not in the adult. The retinal lesion was detectable in a child only 5 weeks of age. The primary biochemical defect remains to be defined precisely, but the biochemical abnormality most directly related to the crystal deposition is a high concentration of cystine within the cells rather than in the plasma. The cystine concentration of cystinotic leukocytes is 80 times normal and of cystinotic fibroblasts grown in culture is 100 times normal. Heterozygotes show modest increases in concentration of cystine in both cell types. Cystine may be compartmentalized within cells of these children since it separates with a granular fraction on high speed centrifugation and is incapable of supplying the nutritional requirements for cystine when affected fibroblasts are cultured in vitro on a cystine free media. Experimental treatment of these children with D-penicillamine or with a synthetic diet low in cystine and methionine decreased the concentration of cystine in plasma to 1/2 and 1/3 of normal values, respectively, but failed to alter either the clinical course or the intracellular concentration of cystine.

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