TREATMENT

The treatment of cystinosis can be divided into symptomatic and pathophysiologic management.

Symptomatic management addresses the numerous complications of cystine accumulation in different organ systems. The major early complication is renal FS, as described previously, which must be treated with replacement of wasted fluids, electrolytes (including potassium, phosphate, and bicarbonate), vitamin D, and carnitine.

To address the many additional complications listed previously, follow-up care should include measurement of serum creatinine concentration, thyroid panels, insulin levels, lipid panels, testosterone, and sex hormone levels; glucose tolerance tests; electromyography; barium swallow studies; computed tomography of the brain and chest (for detecting calcification of cerebral and other major vessels); renal ultrasonography (to assess for nephrocalcinosis); and pulmonary function tests.

As renal disease progresses, renal replacement therapy is commonly required. Transplantation of both living donor and cadaveric kidneys has led to excellent outcomes, with no recurrence of renal FS in the donor kidney.

Pathophysiologic management, meanwhile, involves the use of cystine-depleting agents to actually slow disease progression. Cysteamine, an aminothiol, reacts with cystine to form cystine-cysteamine mixed disulfide and cysteine, which exit the lysosome via lysine and cysteine transporters, respectively. As a result, cysteamine depletes intracellular cystine levels by 90%. Oral cysteamine is indicated for all patients, independent of age and transplantation status. Meanwhile, topical cysteamine eye drops can also dissolve corneal crystals and ameliorate the photophobia of cystinosis within a few weeks. Regular measurement of the leukocyte cystine level documents the efficacy of treatment.

PROGNOSIS

The use of cystine-depleting therapy has revolutionized the prognosis of NC. With prompt and compliant cysteamine treatment, many children do not develop renal failure until their second or third decade of life. The severity of the various complications depends largely on genetic heterogeneity and compliance with medical therapy. Most complications are preventable and possibly even reversible with optimal treatment. Newborn screening for early diagnosis will further advance the treatment of cystinosis.