van der Knaap M S, Jakobs C, Hoffmann G F, Nyhan W L, Renier W O, Smeitink J A, Catsman-Berrevoets C E, Hjalmarson O, Vallance H, Sugita K, Bowe C M, Herrin J T, Craigen W J, Buist N R, Brookfield D S, Chalmers R A
Department of Child Neurology, Free University Hospital, Amsterdam, The Netherlands.
Ann Neurol. 1999 Jan;45(1):111-9. doi: 10.1002/1531-8249(199901)45:1<111::aid-art17>3.0.co;2-n.
D-2-Hydroxyglutaric aciduria has been observed in patients with extremely variable clinical symptoms, creating doubt about the existence of a disease entity related to the biochemical finding. An international survey of patients with D-2-hydroxyglutaric aciduria was initiated to solve this issue. The clinical history, neuroimaging, and biochemical findings of 17 patients were studied. Ten of the patients had a severe early-infantile-onset encephalopathy characterized by epilepsy, hypotonia, cerebral visual failure, and little development. Five of these patients had a cardiomyopathy. In neuroimaging, all patients had a mild ventriculomegaly, often enlarged frontal subarachnoid spaces and subdural effusions, and always signs of delayed cerebral maturation. In all patients who underwent neuroimaging before 6 months, subependymal cysts over the head or corpus of the caudate nucleus were noted. Seven patients had a much milder and variable clinical picture, most often characterized by mental retardation, hypotonia, and macrocephaly, but sometimes no related clinical problems. Neuroimaging findings in 3 patients variably showed delayed cerebral maturation, ventriculomegaly, or subependymal cysts. Biochemical findings included elevations of D-2-hydroxyglutaric acid in urine, plasma, and cerebrospinal fluid in both groups. Cerebrospinal fluid gamma-aminobutyric acid was elevated in almost all patients investigated. Urinary citric acid cycle intermediates were variably elevated. The conclusion of the study is that D-2-hydroxyglutaric aciduria is a distinct neurometabolic disorder with at least two phenotypes.
D-2-羟基戊二酸尿症患者的临床症状差异极大，这让人怀疑是否存在与该生化发现相关的疾病实体。为此启动了一项针对D-2-羟基戊二酸尿症患者的国际调查。对17例患者的临床病史、神经影像学和生化检查结果进行了研究。其中10例患者患有严重的早发性婴儿脑病，其特征为癫痫、肌张力减退、脑性视力障碍和发育迟缓。其中5例患者患有心肌病。在神经影像学检查中，所有患者均有轻度脑室扩大，额叶蛛网膜下腔和硬膜下积液常增多，且均有脑成熟延迟的迹象。在6个月前接受神经影像学检查的所有患者中，均发现尾状核头部或体部有室管膜下囊肿。7例患者的临床表现要轻得多且各不相同，最常见的表现为智力发育迟缓、肌张力减退和巨头畸形，但有时也无相关临床问题。3例患者的神经影像学检查结果不同程度地显示脑成熟延迟、脑室扩大或室管膜下囊肿。生化检查结果包括两组患者的尿液、血浆和脑脊液中D-2-羟基戊二酸水平升高。几乎所有接受调查的患者脑脊液中的γ-氨基丁酸水平均升高。尿中柠檬酸循环中间产物水平也不同程度升高。该研究的结论是，D-2-羟基戊二酸尿症是一种独特的神经代谢紊乱疾病，至少有两种表型。
