X-linked creatine transporter deficiency: clinical aspects and pathophysiology.
Creatine transporter deficiency was discovered in 2001 as an X-linked cause of intellectual disability characterized by cerebral creatine deficiency. This review describes the current knowledge regarding creatine metabolism, the creatine transporter and the clinical aspects of creatine transporter deficiency. The condition mainly affects the brain while other creatine requiring organs, such as the muscles, are relatively spared. Recent studies have provided strong evidence that creatine synthesis also occurs in the brain, leading to the intriguing question of why cerebral creatine is deficient in creatine transporter deficiency. The possible mechanisms explaining the cerebral creatine deficiency are discussed. The creatine transporter knockout mouse provides a good model to study the disease. Over the past years several treatment options have been explored but no treatment has been proven effective. Understanding the pathogenesis of creatine transporter deficiency is of paramount importance in the development of an effective treatment.
Department of Clinical Genetics, VU University Medical Center, P.O. Box 7057, 1007 MB, Amsterdam, The Netherlands, jm.vandekamp@vumc.nl.
Jiddeke M
JM
van de Kamp
Grazia M
GM
Mancini
Gajja S
GS
Salomons
D000592:Amino Acid Metabolism, Inborn Errors / Q000175:diagnosis / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D000818:Animals; D020739:Brain Diseases, Metabolic, Inborn / Q000150:complications / Q000235:genetics / Q000503:physiopathology*; D003401:Creatine / Q000172:deficiency* / Q000235:genetics; D040181:Genetic Diseases, X-Linked / Q000235:genetics*; D006801:Humans; D008607:Intellectual Disability / Q000209:etiology* / Q000235:genetics; D026901:Membrane Transport Proteins / Q000172:deficiency* / Q000235:genetics; D038901:X-Linked Intellectual Disability / Q000150:complications / Q000235:genetics / Q000503:physiopathology*; D051379:Mice; D050480:Plasma Membrane Neurotransmitter Transport Proteins / Q000172:deficiency* / Q000235:genetics
D026901:Membrane Transport Proteins; D050480:Plasma Membrane Neurotransmitter Transport Proteins; C080679:creatine transporter; D003401:Creatine