Deutsch Stephen I, Rosse Richard B, Long Katrice D, Gaskins Brooke, Mastropaolo John
Mental Health Service Line, Department of Veterans Affairs Medical Center, 50 Irving St, NW, Washington, DC 20422, USA.
Clin Neuropharmacol. 2006 Nov-Dec;29(6):361-3. doi: 10.1097/01.WNF.0000236767.46526.1F.
Sarcosinemia is a relatively rare autosomal recessive disorder that has a varied phenotypic presentation; rarely, it is associated with neurodevelopmental and neurological abnormalities. Sarcosine is a key intermediate in 1-carbon metabolism, and its elevation in blood and urine could reflect a deficient pool size of activated 1-carbon units. Sarcosine is also an inhibitor of an important glycine transporter in brain and is under clinical investigation as a glycinergic intervention for conditions with presumed N-methyl-d-aspartate (NMDA) receptor hypofunction, such as schizophrenia. Preclinical research with a mouse model that is used to study pharmacological modulation of endogenous NMDA receptor-mediated tone may clarify, at least in some instances, varied phenotypic presentations of sarcosinemia that are often clinically benign. Sarcosine's effectiveness as a glycinergic agonist intervention for NMDA receptor hypofunction depends on an interaction between genetic background and a stressful environmental insult. Thus, neurodevelopmental and neurological abnormalities may manifest rarely in sarcosinemia in the context of relatively unique genetic factors and fetal insult or stress.
肌氨酸血症是一种相对罕见的常染色体隐性疾病，其表型表现多样；极少数情况下，它与神经发育和神经异常有关。肌氨酸是一碳代谢的关键中间体，其在血液和尿液中的升高可能反映了活性一碳单位池的大小不足。肌氨酸也是大脑中一种重要甘氨酸转运体的抑制剂，目前正在作为一种甘氨酸能干预措施进行临床研究，用于治疗假定存在N-甲基-D-天冬氨酸（NMDA）受体功能减退的疾病，如精神分裂症。使用小鼠模型进行的临床前研究用于研究内源性NMDA受体介导的张力的药理学调节，至少在某些情况下，可能会阐明通常临床上为良性的肌氨酸血症的不同表型表现。肌氨酸作为NMDA受体功能减退的甘氨酸能激动剂干预措施的有效性取决于遗传背景和应激性环境损伤之间的相互作用。因此，在相对独特的遗传因素以及胎儿损伤或应激的情况下，神经发育和神经异常可能在肌氨酸血症中很少表现出来。
