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Project Description

Cystinosis (Online Mendelian Inheritance in Man [OMIM] 219800) is a rare lysosomal storage disorders (LSDs) with incidence of 1:100,000 -200,000 and is characterized by the tissue accumulation of cystine crystals leading to multiple organ dysfunction (1). It is an autosomal recessive metabolic disorder caused by mutations in the CTNS gene, which encodes a 7-transmembrane domain protein, a lysosomal cystine transporter (2). Clinically, there are 3 types of cystinosis, (i) infantile nephropathic cystinosis who have kidney as well as systemic involvement and is most common and severe form, accounting for 95% of all cases (ii) intermediate which is characterised by a late-onset variant of nephropathic cystinosis and (iii) non-nephropathic cystinosis (very rare). Kidneys are one of the earliest organs involved and symptoms begin in early infancy with failure to thrive, polyuria and bony deformities (3). The laboratory test shows features of Fanconi syndrome (metabolic acidosis with hypokalemia and urine showing glucosuria, aminoaciduria and proteinuria- renal Fanconi syndrome). If untreated, it causes end‑stage kidney disease (ESKD) by the end of the first decade and cystine accumulation in other organs causing extrarenal complications, such as hypothyroidism, diabetes mellitus, and myopathy, among others.  The only treatment available for cystinosis is cysteamine, an aminothiol that depletes lysosomal cystine by entering the lysosome and generating cysteine and a cysteine-cysteamine mixed disulfide (4). The cysteine-cysteamine mixed disulfide exits the lysosome by the cationic amino acid transporter, PQLC2, while free cysteine has been found to be freely removed, most likely via a cysteine-specific lysosomal transport system, thus by-passing the need for cystinosin (5). For the therapy to work and to prevent or delay other complications of the disease, it needs to be started early by 3-6 months of age and is given life-long.  Cysteamine is not available in India and the drug needs to be imported which is prohibitively expensive.