The History of Cystinosis: Lessons for Clinical Management

Abstract

Cystinosis is a rare disorder, and, accordingly, progress on the understanding and treatment of this disease has been relatively slow. Although cystinosis was identified over 100 years ago, the history of cystinosis is marked by a few sudden leaps forward in our understanding rather than by a sustained research effort fuelled by the larger research community. Major conceptual break-throughs include (a) its discovery in 1903, (b) recognition of the renal Fanconi syndrome, (c) realization that tissue accumulation of cystine reflects a defective channel in the lysosomal membrane, (d) translation of this discovery to trials of cysteamine, (e) discovery of the CTNS gene, and (f) report of successful stem cell therapy in the cystinotic mouse. This paper focuses on the importance management lessons from these milestones and the potential new therapeutic strategies which may be looming in the near future.

Cistinosis en pacientes adolescentes y adultos: Recomendaciones para la atención integral de la cistinosis

“…Esto explica la necesidad de administrar el fármaco cada 6 horas, toma nocturna incluida 101-102 (tabla 3). Incluso cuando el diagnóstico de cistinosis es tardío, la administración de cisteamina ha demostrado beneficios clínicos 4,6,98 . En pacientes en seguimiento con dosis estables, se recomienda la monitorización cada 6 meses.…”

Substrate Reduction Therapy in Four Patients with Milder CLN1 Mutations and Juvenile-Onset Batten Disease Using Cysteamine Bitartrate

“…The beneficial effect of Cystagon in the treatment of cystinosis is due to its ability to decrease/clear the abnormal lysosomal accumulation of cystine associated with this disorder (Goodyer 2011).…”

Cysteamine (Cystagon(R)) adherence in patients with cystinosis in Spain: successful in children and a challenge in adolescents and adults

“…Cysteamine treatment, which has been available since the 1980s, is able to preserve renal function and delay progression to renal failure [ 21 ] and later reduce systemic involvement of the disease [ 9 , 10 ]. Oral cysteamine is able to achieve leucocyte cystine depletion of up to 95% [ 22 , 23 ] and reduce the cystine parenchymal tissue content when adherence is consistent [ 21 ], with substantial beneficial effects on renal and extra-renal co-morbidities [ 4 – 7 ] and patient life expectancy [ 16 , 17 ]. Data on leucocyte cystine levels were not included in this study for their concordance with patient self-report information on adherence to be evaluated; however, the overall outcome of our cohort of cystinotic patients concurs with data of other recently published series [ 6 , 16 , 17 ].…”

“…Oral cysteamine is able to achieve leucocyte cystine depletion of up to 95% [ 22 , 23 ] and reduce the cystine parenchymal tissue content when adherence is consistent [ 21 ], with substantial beneficial effects on renal and extra-renal co-morbidities [ 4 – 7 ] and patient life expectancy [ 16 , 17 ]. Data on leucocyte cystine levels were not included in this study for their concordance with patient self-report information on adherence to be evaluated; however, the overall outcome of our cohort of cystinotic patients concurs with data of other recently published series [ 6 , 16 , 17 ]. Indeed, at the time of the study, 40% of cystinotic patients in this series were adults, a finding that reflects the impact of early diagnosis and cysteamine prescription in most cases.…”

“…This changing scenario in cystinosis poses new challenges such as long-term compliance with a lifelong treatment [ 7 ], a difficult task in patients who take multiple medications and supplements [ 12 ], are exposed to potential cysteamine-related side effects (gastric intolerance, unpleasant smell and halitosis, among others) [ 13 ] and need to follow an ‘every 6 hour’ (Q6h) [ 14 ] dose schedule of immediately released cysteamine (Cystagon®) [ 15 ]. Last but not least, cystinosis is a good model of a rare ‘paediatric disease’ extending to adult practice [ 4 , 6 , 16 ]; however, few resources are in place to prevent inadequate transition to adult services [ 17 ], management of systemic disease involvement is poor, reference centres are lacking in many countries and, commonly, awareness among adult physicians is low [ 18 ]. Cystinotic patients are often transferred in a suboptimal process to adult services where they feel depressed and ‘lost in the system’ [ 19 ].…”