Heterozygote Detection in Cystinosis, Using Leukocytes Exposed to Cystine Dimethyl Ester

Abstract

CYSTINOSIS, a genetic disorder characterized by autosomal recessive inheritance, typically produces progressive renal disease and death during childhood.^{1 , 2} Many cystinotic tissues, including isolated leukocytes³ and cultured fibroblasts,⁴ have large increases in intracellular cystine content found primarily within the lysosomes.^{5 , 6} Heterozygotes for cystinosis have no crystalline deposits in any tissues.^{1 , 2} In groups of heterozygotes, a small mean increase in intracellular cystine content can be found in isolated leukocytes and cultured skin fibroblasts,^{3 , 4} but some obligate heterozygotes cannot be identified since their fibroblast or leukocyte cystine concentrations are within the normal range.^{1 2 3 4} Subcellular fractionation studies⁷ or selective vacuolation with cysteine-penicillamine disulfide⁸ have . . .