![]() Higher incidence rate is observed in selected populations with detected founder mutations as in the province of Brittany, France (1:26,000 live births) or in the Saguenay-Lac-St-Jean, Quebec, Canada (1:62,500 live births). The overall incidence rates reported in France, Australia, Germany, Denmark and Sweden were 1:167,000, 1: 192,000, 1: 179,000, 1:115,000 and 1:260,000 live births, respectively. Nationwide birth prevalence data concerning cystinosis are only reported in few populations. In the current review, we describe the clinical spectrum of the disease, the diagnostic and management protocols and the anticipated advances in the near future. Although cystinosis is a monogenic disease, it has three major clinical presentations depending on the severity of mutations affecting the CTNS gene: the infantile nephropathic form (MIM: 219800, ORPHA411629), the juvenile nephropathic form (MIM: 219900, ORPHA411634) and the ocular non-nephropathic form (MIM: 219750, ORPHA411641). Ĭystinosis is a systemic disease and cystine crystals, the pathologic landmark, accumulate in all body cells and tissues. The aminothiol cysteamine, used for the treatment of cystinosis for over 20 years now, can deplete the intralysosomal cystine through the reduction of cystine, and the formation of cysteine and a cysteamine-cysteine mixed disulfide which exits the lysosome via the cationic amino acid transporter PQLC2, thus bypassing the original genetic and biochemical defects of the disease. Cystinosis is one of the few rare diseases having a specific treatment. Cystinosis (ORPHA213) is a rare autosomal recessive lysosomal storage disorder in which the amino acid cystine accumulates in the lysosomes of cells. The currently used term “cystinosis” is a modification from the German term “Cystindiathese” or “hereditary cystine disease” which was initially used by Emil Abderhalden to describe the disease in 1903 and was modified in the English literature to “cystine disease” then “cystinosis”. Hence, cystinosis was also recognized in the literature as the Lignac-Fanconi syndrome. Guido Fanconi (1892–1979), the Swiss pediatrician, also substantially contributed to the understanding of cystinosis by explaining the urinary substance losing nature of the disease. This is why cystinosis was initially termed as the Abderhalden-Kaufmann-Lignac syndrome. The Dutch pathologist George Lignac (1891–1954) was the first to provide a clear systematic description of the disease in 1924, and the first to associate cystinosis with its major clinical manifestations such as rickets, renal disease and growth retardation. This patient died at the age of 21 months with massive cystine accumulation in multiple organs that were discovered at the postmortem examination. Abderhalden referred to a child initially encountered by Eduard Kaufmann, Basel, Switzerland (1860–1931). In the current review we will discuss the most important clinical features of the disease, advantages and disadvantages of the current diagnostic and therapeutic options and the main topics of future research in cystinosis.Ĭystinosis was first described in literature in 1903 by the Swiss biochemist Emil Abderhalden (1877–1950) as the familial cystine accumulation disease. Several lines of treatment are available for cystinosis including the cystine depleting agent cysteamine, renal replacement therapy, hormonal therapy and others however, no curative treatment is yet available. Leucocyte cystine assay is the cornerstone for both diagnosis and therapeutic monitoring of the disease. Other affected organs include eyes, thyroid, pancreas, gonads, muscles and CNS. The kidneys are initially affected during the first year of life through proximal tubular damage followed by progressive glomerular damage and end stage renal failure during mid-childhood if not treated. Defective cystinosin function leads to intra-lysosomal cystine accumulation in all body cells and organs. ![]() ![]() It is an autosomal recessive lysosomal storage disorder caused by mutations in the CTNS gene encoding for the carrier protein cystinosin, transporting cystine out of the lysosomal compartment. Cystinosis is the most common hereditary cause of renal Fanconi syndrome in children. ![]()
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