Kuhara Tomiko
Division of Human Genetics, Medical Research Institute, Kanazawa Medical University, Uchinada-machi, Kahoku-gun, Ishikawa, Japan.
J Chromatogr B Analyt Technol Biomed Life Sci. 2007 Aug;855(1):42-50. doi: 10.1016/j.jchromb.2007.03.031. Epub 2007 Mar 31.
Early diagnosis and treatment are critical for patients with inborn errors of metabolism (IEMs). For most IEMs, the clinical presentations are variable and nonspecific, and routine laboratory tests do not indicate the etiology of the disease. A diagnostic procedure using highly sensitive gas chromatography-mass spectrometric urine metabolome analysis is useful for screening and chemical diagnosis of IEM. Metabolite analysis can comprehensively detect enzyme dysfunction caused by a variety of abnormalities. The mutations may be uncommon or unknown. The lack of coenzymes or activators and the presence of post-translational modification defects and subcellular localization abnormalities are also reflected in the metabolome. This noninvasive and feasible urine metabolome analysis, which uses urease-pretreatment, partial adoption of stable isotope dilution, and GC/MS, can be used to detect more than 130 metabolic disorders. It can also detect an acquired abnormal metabolic profile. The metabolic profiles for two cases of non-inherited phenylketonuria are shown. In this review, chemical diagnoses of hyperphenylalaninemia, phenylketonuria, hyperprolinemia, and lactic acidemia, and the differential diagnosis of beta-ureidopropionase deficiency and primary hyperammonemias including ornithine transcarbamylase deficiency and carbamoylphosphate synthetase deficiency are described.
对于患有先天性代谢缺陷（IEMs）的患者而言，早期诊断和治疗至关重要。对于大多数IEMs，临床表现具有多样性且缺乏特异性，常规实验室检查无法明确疾病病因。采用高灵敏度气相色谱 - 质谱联用尿液代谢组分析的诊断方法，对IEM的筛查和化学诊断很有用。代谢物分析能够全面检测由多种异常情况导致的酶功能障碍。这些突变可能并不常见或尚不明确。辅酶或激活剂的缺乏以及翻译后修饰缺陷和亚细胞定位异常的存在也会在代谢组中有所体现。这种采用尿素酶预处理、部分采用稳定同位素稀释以及气相色谱/质谱联用的非侵入性且可行的尿液代谢组分析，可用于检测130多种代谢紊乱。它还能检测获得性异常代谢谱。展示了两例非遗传性苯丙酮尿症的代谢谱。在本综述中，描述了高苯丙氨酸血症、苯丙酮尿症、高脯氨酸血症和乳酸血症的化学诊断，以及β-脲基丙酸酶缺乏症和包括鸟氨酸转氨甲酰酶缺乏症和氨甲酰磷酸合成酶缺乏症在内的原发性高氨血症的鉴别诊断。
