DOCOSAHEXAENOIC ACID THERAPY IN PEROXISOMAL DISORDERS

过氧化物酶体生物发生障碍（PBD）包括齐薇格综合征，婴儿Refsum和新生儿肾上腺白质营养不良导致智力迟钝，视网膜色素变性，并导致早期死亡。二十二碳六烯酸（DHA）是视网膜和大脑的关键成分。已经证明，过氧化物酶体的DHA合成和血浆水平在PBD中大大降低。马丁内斯等人（Neurology; 1993;43:1389-97）通过补充DHA乙酯提高了血浆水平，这导致了一个儿童的临床改善。我们和其他人已经证明，口服DHA可以提高血浆水平。这项研究的目的是测试DHA的补充是否可以改变临床病程，特别是改善这些疾病中受影响的视觉和神经功能。该研究是一项双盲、随机、安慰剂对照研究。计划招募60名患者。在基线时对PBD儿童进行神经学评估、神经心理学测量和眼科学研究，包括视网膜电图和视觉诱发电位。然后他们被分配到治疗组或安慰剂组。治疗方法是服用微胶囊形式的DHA，口服剂量约为100mg /kg/天。该制剂可与食物混合，耐受性良好。安慰剂是一种植物油混合物，以类似DHA制剂的方式制备。儿童在一年后返回，并使用相同的电池进行重复评估。

The disorders of peroxisome biogenesis (PBD) which include Zellweger syndrome, infantile Refsum, and neonatal adrenoleukodystrophy result in mental retardation, retinitis pigmentosa, and lead to early death. Docosahexaenoic acid (DHA) is a key component of retina and brain. It has been demonstrated that peroxisomal synthesis of DHA and plasma levels are greatly diminished in PBD. Martinez et al (Neurology 1993;43:1389-97) increased plasma levels by supplementation with DHA ethyl ester and this resulted in clinical improvement in one child. We and others have demonstrated that plasma levels could be raised with the oral administration of DHA. The aim of the study is to test if the supplementation of DHA can alter the clinical course specifically improve the visual and neurologic function affected in these disorders. The study is a double-blinded, randomized, placebo-controlled study. It is planned to enroll 60 patients. Children with PBD are evaluated at baseline with neurologic assessment, neuropsychologic measures, and ophthalmologic studies including electroretinogram and visual evoked potentials. They are then assigned to treatment or placebo. Treatment is a microencapsulated form of DHA that is taken orally at a dose of approximately 100 mg/kg/day. This preparation can be mixed with food and is well tolerated. The placebo is a mixture of vegetable oil prepared in a similar fashion to the DHA preparation. Children return in one year and undergo repeat evaluation using the same battery.