Cystinosis: practical tools for diagnosis and treatment

Abstract

Cystinosis is the major cause of inherited Fanconi syndrome, and should be suspected in young children with failure to thrive and signs of renal proximal tubular damage. The diagnosis can be missed in infants, because not all signs of renal Fanconi syndrome are present during the first months of life. In older patients cystinosis can mimic idiopathic nephrotic syndrome due to focal and segmental glomerulosclerosis. Measuring elevated white blood cell cystine content is the corner stone for the diagnosis. The diagnosis is confirmed by molecular analysis of the cystinosin gene. Corneal cystine crystals are invariably present in all patients with cystinosis after the age of 1 year. Treatment with the cystine depleting drug cysteamine should be initiated as soon as possible and continued lifelong to prolong renal function survival and protect extra-renal organs. This educational feature provides practical tools for the diagnosis and treatment of cystinosis.

Fig. 1

Flowchart for the diagnosis and follow-up of patients with cystinosis

Fig. 2

Cystine depleting action of cysteamine. In the left panel, a normal lysosome is presented; cystine located in the lysosomes is exported via cystinosin. In the cytosol, cystine is reduced to two cysteine residues. The middle panel shows a cystinotic lysosome, where cystinosin is absent (or dysfunctional), resulting in increased levels of lysosomal cystine. Upon cysteamine treatment in the cystinotic lysosome, cystine is degraded into cysteine and cysteine–cysteamine, as presented in the right panel. Both degradation products can be exported via cysteine and as yet unidentified “system c” transporters, encompassing the defective cystinosin