Lysosomal cystine transport in cystinosis variants and their parents

Abstract

Children with nephropathic cystinosis store 50 to 100 times normal amounts of free cystine in many cells and display negligible lysosomal cystine transport in their leucocytes and cultured fibroblasts. A patient with intermediate (adolescent) cystinosis exhibited a similar deficiency of egress out of fibroblast lysosome-rich granular fractions. Another individual with benign (adult) cystinosis accumulated only 2.85 nmol 1/2 cystine/mg leucocyte protein, or 20-50% of the amount stored in nephropathic cystinosis leucocytes. His leucocyte granular fractions also displayed substantial residual cystine-carrying capacity, as determined by measurement of lysosomal cystine counter-transport. We conclude that the variant forms of cystinosis represent a continuum of lysosomal cystine storage, with the varied clinical presentation depending on the amount of residual cystine-carrying capacity, genetic predispositions, and differential tissue susceptibilities.