Cystinosis and the Kidney

Abstract

Cystinosis is a recessively inherited metabolic disorder characterized biochemically by a raised intracellular concentration of cystine. This increased concentration of cystine, which appears to be stored in lysosomes, leads to crystal deposition in the bone marrow, cornea, conjunctiva, and internal organs, especially the kidney. In spite of this generalized crystal deposition, the major symptomatology of cystinosis is limited to the kidney. At birth and for the first six months of life these infants appear normal, but with careful assessment of renal tubular function, abnormalities, especially of amino acid handling, can be demonstrated (1). Often the first signs of illness are polyuria and polydipsia because of defective water handling which can also lead to dehydration and recurrent unexplained fevers. By one year of age, growth retardation, acidosis, and rickets are present and are paralleled by the appearance of the Fanconi syndrome manifested by glucosuria, phosphaturia, bicarbonaturia and generalized aminoaciduria. Cystine excretion by the kidney is increased in proportion to the increase in the other amino acids which differs from cystinuria where only cystine and dibasic amino acid excretion is increased. In addition, these patients show a marked tendency to hypokalemia which can be exacerbated with fatal consequences during glucose loading. On this background of tubular dysfunction, there is superimposed a progressive impairment of glomerular function.