AN INFANTILE AUTISTIC SYNDROME CHARACTERISED BY THE PRESENCE OF SUCCINYLPURINES IN BODY FLUIDS
AN INFANTILE AUTISTIC SYNDROME CHARACTERISED BY THE PRESENCE OF SUCCINYLPURINES IN BODY FLUIDS
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一种以体液中存在琥珀酰嘌呤为特征的婴儿自闭症候群
DOI：
10.1016/s0140-6736(84)91505-8
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发表时间：
1984
期刊：
影响因子：
--
通讯作者：
V. Berghe
中科院分区：
文献类型：
--
作者：
JaakJaeken Georges;V. Berghe
在3名患有严重精神运动障碍和自闭症的儿童的体液中发现了琥珀酰腺苷和琥珀酸氨基咪唑甲酰胺核苷，其中包括一名兄妹。采用酸解、阴离子交换层析和紫外光谱等方法对两种琥珀酸嘌呤进行了鉴定。两种化合物在脑脊液中的浓度均在100mmoL/L左右，在血浆中的浓度在5~10mmoL/L之间，在尿中的浓度在μ/L范围内。在对照组的脑脊液和血浆中未检测到琥珀酸嘌呤，但在正常尿液中可能有微量。这些化合物是腺苷琥珀酸裂解酶的两种底物--腺苷琥珀酸裂解酶和琥珀酸氨基咪唑甲酰胺核苷的胞内代谢物去磷酸化的衍生物。它们的存在表明该酶缺乏，该酶参与嘌呤的从头合成和从一磷酸肌苷形成一磷酸腺苷。一名患者的检测显示，肝脏的腺苷琥珀酸酶活性明显降低，肾脏没有活性。这两种琥珀酸嘌呤在脑脊液中的积累表明，大脑中也存在这种酶的缺陷，这可能是一组遗传决定的自闭症儿童的基本缺陷。
Succinyladenosine and succinylaminoimidazole carboxamide riboside were found in body fluids from 3 children, including a brother and sister, with severe psychomotor delay and autism. Both succinylpurines were identified by acid hydrolysis, anion-exchange chromatography, and ultraviolet spectrophotometry. Concentrations of both compounds were around 100 μmol/l in cerebrospinal fluid, between 5 and 10 μmol/l in plasma, and in the mmol/l range in urine. Succinylpurines were undetectable in cerebrospinal fluid and plasma from controls but there might be trace amounts in normal urine. The compounds are dephosphorylated derivatives of the intracellular metabolites adenylosuccinate and succinylaminoimidazole carboxamide ribotide, the two substrates of adenylosuccinase (adenylosuccinate lyase, EC 4.3.2.2). Their presence indicates a deficiency of this enzyme, which is involved in both de novo synthesis of purines and the formation of adenosine monophosphate from inosine monophosphate. Assays in one patient revealed markedly decreased adenylosuccinase activity in the liver and absence of activity in the kidney. The accumulation of both succinylpurines in the cerebrospinal fluid suggests that there is also a deficiency of this enzyme in the brain and that it may be the basic defect in a subgroup of children with genetically determined autism.