Effects of long-term cysteamine treatment in patients with cystinosis

Abstract

Cystinosis is a rare autosomal-recessive lysosomal storage disease with high morbidity and mortality. It is caused by mutations in the CTNS gene that encodes the cystine transporter, cystinosin, which leads to lysosomal cystine accumulation. Patients with infantile nephropathic cystinosis, the most common and most severe clinical form of cystinosis, commonly present with renal Fanconi syndrome by 6-12 months of age, and without specific treatment, almost all will develop end-stage renal disease (ESRD) by 10-12 years of age. Early corneal cystine crystal deposition is a hallmark of the disease. Cystinosis also presents with gastrointestinal symptoms (e.g., vomiting, decreased appetite, and feeding difficulties) and severe growth retardation and may affect several other organs over time, including the eye, thyroid gland, gonads, pancreas, muscles, bone marrow, liver, nervous system, lungs, and bones. Cystine-depleting therapy with cysteamine orally is the only specific targeted therapy available for managing cystinosis and needs to be combined with cysteamine eye drops for corneal disease involvement. In patients with early treatment initiation and good compliance to therapy, long-term cysteamine treatment delays progression to ESRD, significantly improves growth, decreases the frequency and severity of extrarenal complications, and is associated with extended life expectancy. Therefore, early diagnosis of cystinosis and adequate life-long treatment with cysteamine are essential for preventing end-organ damage and improving the overall prognosis in these patients.

Skeletal Consequences of Nephropathic Cystinosis

“…As improved medical treatment has increased life expectancy of individuals with nephropathic cystinosis into adulthood, late complications of the disease have been recognized, with skeletal health an emerging concern. We report here a systematic evaluation of skeletal manifestations of nephropathic cystinosis, in a large series of both non‐transplanted and post‐transplanted subjects seen consecutively at the NIH Clinical Center.…”

Clinical trials in mitochondrial disorders, an update

“…Cysteamine bitartrate is an aminothiol used as an approved therapy for nephropathic cystinosis [ 19 ]. Cysteamine breaks the disulfide bond of cystine, forming cysteine–cysteamine disulfide and cysteine, the latter of which is a precursor of glutathione biosynthesis [ 20 , 21 ].…”

Precision Medicine for Lysosomal Disorders

“…However, eliglustat does not cross the BBB, limiting its effects on the neuropathic forms of the disease. Another example is cysteamine, which is the treatment of choice for nephropathic cystinosis since it delays progression of the renal and extrarenal manifestations and has a strong impact on survival rates [64]. Disease progression in NPC patients has been proven to stabilize with intrathecal 2-hydroxypropyl-β-cyclodextrin (HP-β-CD) since it does not cross the BBB [65].…”