Cystinosis

Abstract

Cystinosis, an autosomal recessive lysosomal storage disease of cystine, manifests clinically with endstage renal disease, short stature, corneal crystals, and other organ involvement. There are three clinical forms of cystinosis, the most common being infantile or nephropathic cystinosis. Affected patients present between 6 months and 2 years of age with either failure to thrive or some other manifestations of the renal Fanconi syndrome, such as dehydration, acidosis, electrolyte imbalance, glucosuria, or hypophosphatemic rickets. Renal glomerular damage is progressive, leading to endstage renal failure. Linear growth and weight are adversely affected, while head growth is spared. Ophthalmic complications early in the disease include corneal crystals, which lead to photophobia and “foreign body sensation.” Later involvement includes visual impairment and corneal erosions. Extrarenal sequelae of cystinosis include abnormalities of thyroid, pancreatic, and testicular function. Muscle weakness, atrophy and life-threatening swallowing dysfunction can be seen in older patients whose lives have been prolonged by renal transplant. All clinical manifestations of cystinosis are attributable to lysosomal cystine storage and its resultant cellular destruction. Diagnosis of nephropathic cystinosis begins with an increased index of suspicion regarding a patient with a typical clinical course. Confirmation of renal Fanconi syndrome should be followed by a slit-lamp examination of the cornea by a trained ophthalmologist looking for the corneal crystals typical of cystinosis. The diagnosis can be verified by detection of elevated cystine levels in cultured fibroblasts or polymorphonuclear leukocytes. Prenatal diagnosis is possible and available. The cellular defect in cystinosis involves the inability of cystine to be transported out of lysosomes. This leads to increased intralysosomal cystine concentration, formation of cystine crystals, and cell death. Cysteamine and phosphocysteamine, cystine-depleting agents, have been in clinical trial since 1978. Administered orally, they attenuate the progressive renal pathology and improve growth. Given topically as eye drops, cysteamine dissolves corneal crystals and relieves photophobia. The long-term efficacy of oral cysteamine in preserving organs other than the kidney is unknown.