Skin storage of cystine and premature skin ageing in cystinosis

Guillet, G.; Sassolas, B.; Fromentoux, S; Gobin, E; Jp, Leroy

doi:10.1016/s0140-6736(05)61267-6

Cited by 18 publications

(9 citation statements)

References 4 publications

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“…Other observed features related to skin, hair and salivary glands have also been reported such as congenital hypopigmentation, premature skin ageing, impaired sweating and salivation and progressive coarse facial features due to subcutaneous cystine infiltration [ 68 ]. According to our experience, not only European patients, but also some patients from other ethnic backgrounds can present with characteristic blond hair and white skin.…”

Section: Introductionmentioning

confidence: 99%

Cystinosis: a review

Elmonem

Veys

Soliman

et al. 2016

Orphanet J Rare Dis

229

244

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Cystinosis is the most common hereditary cause of renal Fanconi syndrome in children. 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. Defective cystinosin function leads to intra-lysosomal cystine accumulation in all body cells and organs. 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. Other affected organs include eyes, thyroid, pancreas, gonads, muscles and CNS. Leucocyte cystine assay is the cornerstone for both diagnosis and therapeutic monitoring of the 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. 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.

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Section: Introductionmentioning

confidence: 99%

Cystinosis: a review

Elmonem

Veys

Soliman

et al. 2016

Orphanet J Rare Dis

229

244

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“…Interestingly, patients with cystinosis exhibit hypopigmentation; Caucasian subjects often have blond hair, blue eyes, and light complexion (13). However, it seems that some patients, in particular, African-American patients, have no hypopigmentation.…”

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confidence: 99%

Cystinosin is a melanosomal protein that regulates melanin synthesis

et al. 2012

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Cystinosis is a rare autosomal recessive disease characterized by cystine crystal accumulation leading to multiorgan dysfunctions and caused by mutation in CTNS. CTNS encodes cystinosin, a cystine/H(+) symporter that exports cystine out of the lysosomes. Patients with cystinosis frequently exhibit blond hair and fair complexion, suggesting an alteration in melanogenesis. However, the pigmentation singularities of these patients have not been studied, and the role of cystinosin in melanogenesis has remained unknown. In our study, a clinical evaluation of 27 patients with cystinosis showed that 44% had a cutaneous pigmentation dilution compared to their relatives. Analysis of the hair melanin content in these patients by HPLC demonstrated a 50% decrease in eumelanin (4360 vs. 9360 ng/mg), and a 2-fold increase in pheomelanin (53 vs. 20 ng/mg), the yellow/red pigments. Cystinosin-deficient mice also showed a 4-fold increase in hair pheomelanin content. In vitro studies showed that cystinosin was located at melanosomes. CTNS silencing led to a 75% reduction of melanin synthesis that was caused by a degradation of tyrosinase by lysosomal proteases. Our results objectify the pigmentation defect in patients with cystinosis. We also identify the role of CTNS in melanogenesis and add a new gene to the list of the genes involved in the control of skin and hair pigmentation.

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“…Cultured cystinotic skin fibroblasts are known to accumulate cystine (16) and are easily available via skin biopsy in patients with cystinosis. Because a metabolic defect caused by cystine accumulation has to be present in all body tissues, we used cystinotic fibroblasts to investigate the energy metabolism in cystinosis.…”

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confidence: 99%

Decreased Intracellular ATP Content and Intact Mitochondrial Energy Generating Capacity in Human Cystinotic Fibroblasts

et al. 2006

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ABSTRACT:Cystinosis is an autosomal recessive lysosomal storage disorder caused by a defect in the lysosomal cystine carrier cystinosin. Cystinosis is the most common cause of inherited Fanconi syndrome leading to renal failure, in which the pathogenesis is still enigmatic. Based on studies of proximal tubules loaded with cystine dimethyl ester (CDME), altered mitochondrial adenosine triphosphate (ATP) production was proposed to be an underlying pathologic mechanism. Thus far, however, experimental evidence supporting this hypothesis in humans is lacking. In this study, energy metabolism was extensively investigated in primary fibroblasts derived from eight healthy subjects and eight patients with cystinosis. Patient's fibroblasts accumulated marked amounts of cystine and displayed a significant decrease in intracellular ATP content. Remarkably, overall energy-generating capacity, activity of respiratory chain complexes, ouabain-dependent rubidium uptake reflecting Na,K-ATPase activity, and bradykinin-stimulated mitochondrial ATP production were all normal in these cells. In conclusion, the data presented demonstrate that mitochondrial energy-generating capacity and Na,K-ATPase activity are intact in cultured cystinotic fibroblasts, thus questioning the idea of altered mitochondrial ATP synthesis as a keystone for the pathogenesis of cystinosis.

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Skin storage of cystine and premature skin ageing in cystinosis

Cited by 18 publications

References 4 publications

Cystinosis: a review

Cystinosis: a review

Cystinosin is a melanosomal protein that regulates melanin synthesis

Decreased Intracellular ATP Content and Intact Mitochondrial Energy Generating Capacity in Human Cystinotic Fibroblasts

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