Limits...
Improving the prognosis of nephropathic cystinosis.

Besouw MT, Levtchenko EN - Int J Nephrol Renovasc Dis (2014)

Bottom Line: Extrarenal organs are also affected, including the thyroid gland, gonads, pancreas, liver, muscle, and brain.Recently, a new delayed-release formulation was marketed, that should be administered every 12 hours.The first studies comparing both cysteamine formulations show comparable results regarding white blood cell cystine depletion (which serves as a measure for cystine accumulation in the body), while a slightly lower daily dose of cysteamine can be used.

View Article: PubMed Central - PubMed

Affiliation: Department of Pediatric Nephrology, University Hospitals Leuven, Belgium ; Laboratory of Pediatrics, Catholic University Leuven, Leuven, Belgium.

ABSTRACT
Cystinosis is an autosomal recessive inherited lysosomal storage disease. It is characterized by generalized proximal tubular dysfunction known as renal Fanconi syndrome and causes end-stage renal disease by the age of about 10 years if left untreated. Extrarenal organs are also affected, including the thyroid gland, gonads, pancreas, liver, muscle, and brain. Treatment consists of administration of cysteamine, resulting in depletion of cystine that is trapped inside the lysosomes. Since cysteamine has a short half-life, it should be administered every 6 hours. Recently, a new delayed-release formulation was marketed, that should be administered every 12 hours. The first studies comparing both cysteamine formulations show comparable results regarding white blood cell cystine depletion (which serves as a measure for cystine accumulation in the body), while a slightly lower daily dose of cysteamine can be used.

No MeSH data available.


Related in: MedlinePlus

Mechanism of lysosomal cystine depletion by cysteamine. Cysteamine enters the lysosome through an unknown transporter and breaks the disulfide bond in cystine. This results in formation of cysteine and a new cysteine-cysteamine mixed disulfide, each of which can exit the lysosome through its own transporter.
© Copyright Policy
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4109637&req=5

f1-ijnrd-7-297: Mechanism of lysosomal cystine depletion by cysteamine. Cysteamine enters the lysosome through an unknown transporter and breaks the disulfide bond in cystine. This results in formation of cysteine and a new cysteine-cysteamine mixed disulfide, each of which can exit the lysosome through its own transporter.

Mentions: Cysteamine uses an unknown transporter to enter the lysosome and subsequently breaks the disulfide bond in cystine. This leads to formation of cysteine, which leaves the lysosome using the cystine transporter, and cysteine-cysteamine disulfide, which leaves the lysosome using the PQLC2 transporter (Figure 1).5,15 Once in the cytosol, cysteine can be further metabolized to form glutathione, one of the cell’s most potent redox buffers. Indeed, in vitro experiments showed that the altered redox status demonstrated in cystinotic cells was corrected by administration of cysteamine, thereby increasing intracellular glutathione levels.16


Improving the prognosis of nephropathic cystinosis.

Besouw MT, Levtchenko EN - Int J Nephrol Renovasc Dis (2014)

Mechanism of lysosomal cystine depletion by cysteamine. Cysteamine enters the lysosome through an unknown transporter and breaks the disulfide bond in cystine. This results in formation of cysteine and a new cysteine-cysteamine mixed disulfide, each of which can exit the lysosome through its own transporter.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4109637&req=5

f1-ijnrd-7-297: Mechanism of lysosomal cystine depletion by cysteamine. Cysteamine enters the lysosome through an unknown transporter and breaks the disulfide bond in cystine. This results in formation of cysteine and a new cysteine-cysteamine mixed disulfide, each of which can exit the lysosome through its own transporter.
Mentions: Cysteamine uses an unknown transporter to enter the lysosome and subsequently breaks the disulfide bond in cystine. This leads to formation of cysteine, which leaves the lysosome using the cystine transporter, and cysteine-cysteamine disulfide, which leaves the lysosome using the PQLC2 transporter (Figure 1).5,15 Once in the cytosol, cysteine can be further metabolized to form glutathione, one of the cell’s most potent redox buffers. Indeed, in vitro experiments showed that the altered redox status demonstrated in cystinotic cells was corrected by administration of cysteamine, thereby increasing intracellular glutathione levels.16

Bottom Line: Extrarenal organs are also affected, including the thyroid gland, gonads, pancreas, liver, muscle, and brain.Recently, a new delayed-release formulation was marketed, that should be administered every 12 hours.The first studies comparing both cysteamine formulations show comparable results regarding white blood cell cystine depletion (which serves as a measure for cystine accumulation in the body), while a slightly lower daily dose of cysteamine can be used.

View Article: PubMed Central - PubMed

Affiliation: Department of Pediatric Nephrology, University Hospitals Leuven, Belgium ; Laboratory of Pediatrics, Catholic University Leuven, Leuven, Belgium.

ABSTRACT
Cystinosis is an autosomal recessive inherited lysosomal storage disease. It is characterized by generalized proximal tubular dysfunction known as renal Fanconi syndrome and causes end-stage renal disease by the age of about 10 years if left untreated. Extrarenal organs are also affected, including the thyroid gland, gonads, pancreas, liver, muscle, and brain. Treatment consists of administration of cysteamine, resulting in depletion of cystine that is trapped inside the lysosomes. Since cysteamine has a short half-life, it should be administered every 6 hours. Recently, a new delayed-release formulation was marketed, that should be administered every 12 hours. The first studies comparing both cysteamine formulations show comparable results regarding white blood cell cystine depletion (which serves as a measure for cystine accumulation in the body), while a slightly lower daily dose of cysteamine can be used.

No MeSH data available.


Related in: MedlinePlus