Development of Screening System for Peroxisomal Disorders Using Dried Spotted Blood and Urine

包括Zellweger综合征在内的过氧酶体疾病筛查系统。发现新生儿肾上腺脑白质营养不良、婴儿Refsum病、X连锁肾上腺脑白质营养不良和单酶缺乏症。(1)建立血清鞘磷脂极长链脂肪酸分析筛查方法。在这些疾病中，木油酸和蜡酸含量极高。用干斑点血提取液进行总脂肪酸分析可用于过氧化物酶体疾病的大规模筛查。(2)尿有机酸分析也可用于过氧化物酶体缺陷性疾病的筛查。二元酸排泄量大，己二酸/己二酸比值高。(3)活检直肠黏膜的生化和形态分析有助于Zellweger综合征的早期诊断。(4)放射性标记的甘油酸氧化和间接免疫荧光过氧化体染色可用于产前诊断。(5)报道了一种新的过氧化酶体疾病变异型Zellweger样综合征。研究了过氧化物酶体缺陷性疾病的遗传异质性。

Screening system of peroxisomal diseases including Zellweger syndrome. Neonatal adrenoleukodystrophy, infantile Refsum's disease, X-linked adrenoleukodystrophy and single enzyme deficiency of peroxisomal beta-oxidation were developed.(1) Screening by verylongchain fatty acid analysis of serum sphingomyelin was established. Lignoceric acid and cerotic acid were extremely high in these disorders. Total fatty acid analysis using extracts from dried spotted blood was applicable to mass screening of peroxisomal diseases.(2) Urinary organic acid analysis was also useful for the screening of peroxisome-deficient disorders. Massive excretion of dicarboxylic acids, high ratio of sebacic acid/adipic acid. Detection of 2-hydroxysebacic acid were the useful marker.(3) Biochemical and morphologic analyses of biopsied rectal mucosa was useful for the early postnatal diagnosis of Zellweger syndrome.(4) Radio labeled lignoceric acid oxidation and indirect immunofluorescent staining of peroxisomes were applicable to the prenatal diagnosis.(5) Zellweger-like syndrome, a new variant form of peroxisomal disease, was reported. Genetic heterogeneity of peroxisome-deficient diseases was investigated.