Cystinosis: the evolution of a treatable disease

Abstract

Cystinosis is a rare autosomal recessive disorder involving lysosomal storage of the amino acid cystine due to a defect in the membrane transport protein, cystinosin. Since the introduction of kidney transplants and the availability of cystine-depleting medical therapy, this previously fatal disease was transformed into a treatable disorder. Renal allografts and medical therapy targeting the basic metabolic defect have altered the natural hisotry of cystinosis so drastically that patients have a life expectancy extending past 50 years. Consequently, early diagnosis and appropriate therapy are critically important. In this article, we offer a review of the manifestations of cystinosis, including the proximal tubular dysfunction of renal Fanconi syndrome, and discuss the prevention and treatment of the disorder’s systemic complications. We focus on the nephropathic forms of cystinosis, aiming to assist nephrologists and other physicians to develop early recognition and appropriate management of cystinosis patients.

Failure to Thrive with Polyuria

“…Cystinosis is a rare autosomal recessive disorder caused by mutations in the CTNS gene (17p13.2) [1][2][3][4][5][6][7]. It is a lysosomal storage disorder whereby there is a defect in the membrane transport protein, cystinosin, causing systemic accumulation of cystine crystals and is the most common cause of inherited renal Fanconi syndrome in children [1,3,4,5].…”

“…It is a lysosomal storage disorder whereby there is a defect in the membrane transport protein, cystinosin, causing systemic accumulation of cystine crystals and is the most common cause of inherited renal Fanconi syndrome in children [1,3,4,5].…”

Mutational Spectrum of the CTNS Gene in Egyptian Patients with Nephropathic Cystinosis

“…The CTNS gene is made up of 12 exons, the last ten encoding for cystinosin, a protein that facilitates cystine transport out of lysosomes. Defective cystinosin-mediated cystine transport leads to the accumulation and crystallization of cystine in cells of different organs, particularly the kidney, cornea, and thyroid (Nesterova and Gahl 2013). Patients with infantile nephropathic cystinosis (OMIM 219800), comprising about 95% of all cases, usually develop renal Fanconi syndrome in the first year of life and renal failure in the first decade if not treated.…”

“…Patients with infantile nephropathic cystinosis (OMIM 219800), comprising about 95% of all cases, usually develop renal Fanconi syndrome in the first year of life and renal failure in the first decade if not treated. Other less common types are the juvenile (OMIM 219900) and the non-nephropathic ocular cystinosis (OMIM 219750) (Nesterova and Gahl 2013).…”

“…Molecular analysis of the CTNS gene confirms the diagnosis and offers the advantage of prenatal diagnosis (Nesterova and Gahl 2013). Detection of corneal cystine crystals by a slit lamp examination is another confirmatory sign, but a rather late one as it is reasonably sensitive close to the second year of life (Soliman et al 2009).…”