Cystine dimethylester model of cystinosis: still reliable?

The ability of cystine dimethylester (CDME) to load lysosomes with cystine has been used to establish the basic defect in cystinosis: defective cystine exodus from lysosomes. Using CDME loading, it has been postulated that cystine accumulation in cystinosis affects mitochondrial ATP production, resulting in defective renal tubular reabsorption. Recent studies in cystinotic fibroblasts, however, show normal adenosine triphosphate (ATP) generation capacity.

The origin of halitosis in cystinotic patients due to cysteamine treatment.

Introduction: Cystinosis is a rare autosomal recessive disorder characterized by the intralysosomal accumulation of cystine. Cysteamine removes cystine from the lysosome and slows down the progression of the disease. One of its side effects is the induction of halitosis, which can interfere with patients' willingness to comply with cysteamine treatment.

Decreased intracellular ATP content and intact mitochondrial energy generating capacity in human cystinotic fibroblasts.

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.

Strict cysteamine dose regimen is required to prevent nocturnal cystine accumulation in cystinosis.

Cystinosis is an autosomal recessive disorder, caused by mutations in the lysosomal cystine carrier cystinosin, encoded by the CTNS gene. The disease generally manifests with Fanconi syndrome during the first year of life and progresses towards end stage renal disease before the age of 10 years. Cysteamine depletes intralysosomal cystine content, postpones the deterioration of renal function and the occurrence of extra-renal organ damage.

Elevated oxidized glutathione in cystinotic proximal tubular epithelial cells.

Cystinosis, the most frequent cause of inborn Fanconi syndrome, is characterized by the lysosomal cystine accumulation, caused by mutations in the CTNS gene. To elucidate the pathogenesis of cystinosis, we cultured proximal tubular cells from urine of cystinotic patients (n = 9) and healthy controls (n = 9), followed by immortalization with human papilloma virus (HPV E6/E7). Obtained cell lines displayed basolateral polarization, alkaline phosphatase activity, and presence of aminopeptidase N (CD-13) and megalin, confirming their proximal tubular origin.