[From gene to disease: cystinosis].
Cystinosis is an autosomal recessive disorder caused by an impaired transport of cystine out of lysosomes. The most severe infantile form of cystinosis starts with Fanconi syndrome at the age of 3-6 months. Untreated patients develop renal failure before the age of 10. The cystinosis gene (CTNS) maps to chromosome 17p13, spans 23 kb and is composed of 12 exons. CTNS encodes a 367 amino acid protein, cystinosin, which is a H(+)-driven lysosomal cystine transporter. It is enigmatic how lysosomal cystine accumulation induces the clinical symptoms. ATP depletion was demonstrated in an experimental model consisting of loading lysosomes with cystine dimethylester. The amino-thiol cysteamine depletes lysosomal cystine content by a disulfide-exchange reaction with cystine. Therapy with cysteamine should be administered as early as possible and continued after a renal transplantation as the extra renal damage still progresses. Improved life expectancy of cystinotic patients requires the attention of internists with a special interest for this rare disorder.
Levtchenko
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EN
Afd. Kindergeneeskunde, Universitair Medisch Centrum St Radboud, Postbus 9101, 6500 HB Nijmegen. e.levtchenko@cukz.umcn.nl
Wilmer
M
M
de Graaf-Hess
A C
AC
van den Heuvel
L P
LP
Blom
H
H
Monnens
L A
LA
D026921:Amino Acid Transport Systems, Neutral; D003543:Cysteamine / Q000008:administration & dosage; D003553:Cystine / Q000378:metabolism; D003554:Cystinosis / Q000188:drug therapy / Q000235:genetics* / Q000503:physiopathology; D005198:Fanconi Syndrome / Q000235:genetics; D017353:Gene Deletion; D006023:Glycoproteins / Q000235:genetics* / Q000502:physiology; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics* / Q000502:physiology; D026901:Membrane Transport Proteins; D051437:Renal Insufficiency / Q000235:genetics
D026921:Amino Acid Transport Systems, Neutral; C111445:CTNS protein, human; D006023:Glycoproteins; D008565:Membrane Proteins; D026901:Membrane Transport Proteins; D003553:Cystine; D003543:Cysteamine