Introduction
Pathogenesis of cystinosis
Cysteamine therapy
Long-term effects of cysteamine therapy
First author, year | Study description | Renal outcomes | Extrarenal complications |
---|---|---|---|
Brodin-Sartorius, 2012 [45] | French study; adults (aged ≥15 years) diagnosed between 1961 and 1995; mean follow-up 24.6 years (n = 86) | • Initiation <5 years of age vs later delayed ESRD onset (mean age at onset 13.4 vs 9.6 years; p < 0.05) • Increased treatment compliance also delayed ESRD onset (p < 0.0001) | • Initiation <5 years of age (vs later or no treatment) reduced rates of hypothyroidism (52.5% vs 73.3% and 96.8%), diabetes (27.5% vs 64.7% and 89.7%), neuromuscular disorders (15% vs 53.6% and 61.1%), and death (5% vs 42.9% and 63.6%) [p < 0.001 for each parameter] |
Broyer, 2008 [46] | Necker Enfants-Malades Hospital series; patients born before 1988; aged 20–39 years (n = 56) | • Initiation <3 years of age vs later delayed ESRD onset (mean age at onset 17.4 vs 9.6 years) | • Initiation <3 years of age vs later: - Improved linear growth (mean height 167 vs 144.5 cm for boys; 153.5 vs 132 cm for girls) and visual acuity (mean 8.5 vs 5) • Reduced rates of glucose intolerance, thyroxine requirements (35.7% vs 88.2%), myopathy (0% vs 38.5%), cerebellar/pyramidal symptoms or mental deterioration (0% vs 35.9%), and hepatosplenic disorders (0% vs 92.3%) |
Gahl, 2007 [16] | US database study; adults (aged 18–45 years) examined between January 1985 and May 2006 (n = 100) | • Treatment for ≥8 years vs <8 years delayed renal transplantation (mean age 14.8 vs 11.0 years) | • Increased duration of therapy (from <10 to >20 years) reduced rates of diabetes (from 28 to 0%), myopathy (from 60 to 0%), pulmonary dysfunction (from 80 to 0%), and death (from 43 to 0%) • Treatment for ≥8 vs <8 years significantly improved mean height (154.7 vs 143.6 cm) and weight (53.2 vs 45.3 kg) parameters, and rates of hypothyroidism (56% vs 87%) and death (8% vs 49%) |
Greco, 2010 [5] | Italian single-center study; patients diagnosed at 3–60 years of age; median follow-up 17.6 years (n = 23) | • Initiation <2.5 years of age vs later improved evolution of renal function (p = 0.006), and decreased risk of CKD stage 3 • Rapid renal function decline prevented by higher cysteamine doses and use of ACEi | • Patients treated more recently (initiated <2.5 years of age) had improved linear growth curves vs older children (p = 0.04) |
Gultekingil Keser, 2014 [47] | Turkish, retrospective, single-center study; patients aged 0.5–29 years; median follow-up 8 years (n = 21) | NR | • Patients with ILC levels <2 vs ≥2 nmol half-cystine/mg protein had reduced rates of short stature (66.6% vs 90.9%), pubertal delay (0% vs 66.6%), hypothyroidism (33.3% vs 54.5%), and diabetes (0% vs 18.1%) |
Nesterova, 2015 [19] | US database study; patients aged 11–48 years examined between 1975 and 2005 (n = 147) | • Treatment compliance was linearly correlated with age at ESRD onset (R2 = 0.997) • Optimal treatment for 1 year preserved 0.9 years of renal glomerular function • Severity of renal Fanconi syndrome (decreased tubular function) was not affected | NR |
Sonies, 2005 [48] | US database study; patients aged 6–45 years examined between February 1987 and March 2004 (n = 101) | NR | • Severity of swallowing dysfunction (muscle atrophy) decreased with increased number of years of treatment |
Tsilou, 2006 [49] | US database study; patients aged 0.5–42 years examined between 1976 and 2004 (n = 208) | NR | • Treatment for >20 vs ≤10 years decreased rate of retinopathy (0% vs 28%) |
Vaisbich, 2010 [50] | Brazilian Multicenter Nephropathic Study; patients aged 1.3–29 years enrolled since 1999 (n = 102) | • Initiation <2 years of age vs later reduced rate of CKD stage II–V (25% vs 77.5%) | • Initiation <2 years vs later: • Improved growth (weight and height) parameters • Reduced rates of hypothyroidism (10% vs 61.7%), diabetes (5% vs 7.8%), muscular weakness (0% vs 6.8%), hepatic dysfunction (0% vs 4.9%), CNS disorders (0% vs 4.9%), and swallowing dysfunction (0% vs 1.9%) |
Viltz, 2013 [51] | Children and adolescents (aged 3–18 years) [n = 46] | NR | • Initiation <2 years vs later improved cognitive function (verbal, performance, and full-scale IQ scores, and spatial-relations test; p < 0.05), but not visual–motor performance scores |