Cysteamine therapy delays the progression of nephropathic cystinosis in late adolescents and adults

Abstract

Nephropathic cystinosis is a multisystem autosomal recessive disease caused by cystine accumulation, which is usually treated by oral cysteamine. In order to determine long-term effects of this therapy, we enrolled 86 adult patients (mean age 26.7 years) diagnosed with nephropathic cystinosis, 75 of whom received cysteamine. Therapy was initiated at a mean age of 9.9 years with a mean duration of 17.4 years. By last follow-up, 78 patients had end-stage renal disease (mean age 11.1 years), 62 had hypothyroidism (mean age 13.4), 48 developed diabetes (mean age 17.1 years), and 32 had neuromuscular disorders (mean age 23.3 years). Initiating cysteamine therapy before 5 years of age significantly decreased the incidence and delayed the onset of end-stage renal disease, and significantly delayed the onset of hypothyroidism, diabetes, and neuromuscular disorders. The development of diabetes and hypothyroidism was still significantly delayed, however, in patients in whom therapy was initiated after 5 years of age, compared with untreated patients. The life expectancy was significantly improved in cysteamine-treated versus untreated patients. Thus, cysteamine decreases and delays the onset of complications and improves life expectancy in cystinosis. Hence, cysteamine therapy should be introduced as early as possible during childhood and maintained lifelong.

Heptahelical protein PQLC2 is a lysosomal cationic amino acid exporter underlying the action of cysteamine in cystinosis therapy

“…Cysteamine therapy remains the most effective treatment for cystinosis (40)(41)(42). The current model, based on early biochemical data (20,43), posits that the compound enters the lysosome and condenses with lysosomal cystine, thus generating a cysteaminecysteine mixed disulfide (MxD) that resembles lysine (Fig.…”

Orphan drug policies and use in pediatric nephrology

“…International consensus recommends the initiation of cysteamine treatment upon diagnosis and continuation of treatment throughout life [29]. Cysteamine delays the onset of renal failure and extra-renal manifestations and improves life expectancy [28,30].…”

Mood and illness experiences of adults with cystinosis

“…4 Cysteamine is effective in preventing organ dysfunction and delays the onset of renal failure, hypothyroidism, diabetes and neuromuscular problems, especially if commenced early in life. 5 However, adherence can be difficult to achieve due to frequent dosing and side-effects including body odor, halitosis and nausea. 6,7 Research to date has primarily focused on the clinical aspects of cystinosis and the search for new therapies with little emphasis on the psychological impact, especially during adulthood.…”