Creatine deficiency syndromes
Creatine deficiency syndromes
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肌酸缺乏综合症
DOI：
10.1007/978-3-540-28785-8_16
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发表时间：
2012
期刊：
影响因子：
--
通讯作者：
John H. Walter
中科院分区：
文献类型：
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作者：
S. Stöckler;G. Salomons;J. Saudubray;G. V. D. Berghe;John H. Walter
肌酸缺乏综合征（CDS）是一组先天性肌酸合成（精氨酸：甘氨酸脒基转移酶（AGAT）（MIM 602360）、胍基乙酸甲基转移酶（GAMT）（MIM 601240）缺乏）和转运[X连锁肌酸转运蛋白（CRTR）]（MIM 300036）缺乏的缺陷。CDS通常表现为脑肌酸缺乏和全面发育迟缓/智力残疾沿着各种神经系统表现。诊断标志物包括GAMT和AGAT缺乏症的体液中乙酸胍浓度分别升高和降低，以及CRTR缺乏症的尿肌酸/肌酐升高。口服补充肌酸导致肌酸合成缺陷的脑肌酸几乎完全恢复：在GAMT缺乏症中，通过补充鸟氨酸和/或饮食精氨酸限制来减少胍基乙酸。在CRTR缺乏症中，补充肌酸、精氨酸和甘氨酸并不能显著改善结局，尽管在单个患者中报告了部分临床改善。据报道，在早期治疗的肌酸合成缺陷患者中，神经发育结局正常。在影响精氨酸和鸟氨酸代谢的疾病中，如鸟氨酸氨基转移酶（OAT）缺乏症、尿素循环缺陷、高氨血症、高鸟氨酸血症、高瓜氨酸尿综合征、Δ（1）-吡咯啉-5-羧酸合成酶缺乏症、甲钴胺合成和线粒体缺陷中，描述了肌酸代谢的继发性变化
Creatine deficiency syndromes (CDS) are a group of inborn errors of creatine synthesis (arginine:glycine amidinotransferase (AGAT) (MIM 602360), guanidinoacetate methyltransferase (GAMT) (MIM 601240) deficiencies), and transport [the X-linked creatine transporter (CRTR)] (MIM 300036) deficiency. CDS typically present with cerebral creatine deficiency and global developmental delay/ intellectual disability along with various neurological manifestations. Diagnostic markers include high and low guanidinoacetate concentrations in body fluids in GAMT and AGAT deficiency, respectively, and increased urinary creatine/creatinine in CRTR deficiency. Oral supplementation of creatine leads to near complete restoration of cerebral creatine in creatine synthesis defects: In GAMT deficiency, reduction of guanidinoacetate is achieved by ornithine supplementation and / or dietary arginine restriction. In CRTR deficiency, creatine, arginine and glycine supplementation does not significantly improve outcome, although partial clinical improvement has been reported in single patients. Normal neurodevelopmental outcome has been reported in early treated patients with creatine synthesis defects. Secondary changes in creatine metabolism have been described in disorders affecting arginine and ornithine metabolism such as ornithine aminotransferase (OAT) deficiency, urea cycle defects, hyperammonemia, hyperornithinemia, homocitrullinuria syndrome, Δ(1)-pyrroline-5-carboxylate synthetase deficiency, in methylcobalamin synthesis and mitochondrial defects