Poll-The B T, Roels F, Ogier H, Scotto J, Vamecq J, Schutgens R B, Wanders R J, van Roermund C W, van Wijland M J, Schram A W
Clinique de Génétique Médicale et INSERM U12, Hôpital des Enfants Malades, Paris, France.
Am J Hum Genet. 1988 Mar;42(3):422-34.
In the present paper two siblings are presented with clinical manifestations very similar to those of patients affected by neonatal adrenoleukodystrophy. In contrast to neonatal adrenoleukodystrophy patients, hepatic peroxisomes in these siblings were enlarged in size and not decreased in number. Accumulation of very-long-chain fatty acids (VLCFA) was associated with an isolated deficiency of the fatty acyl-CoA oxidase, the enzyme that catalyzes the first step of the peroxisomal beta-oxidation. Plasma levels of di- and trihydroxy-coprostanoic acid, phytanic acid, and pipecolic acid were normal; furthermore, acyl-CoA:dihydroxyacetone phosphate acyltransferase activity in cultured fibroblasts was also found to be normal. The clinical, biochemical, and cytochemical features found in these two siblings are compared with those seen in two other disorders characterized by the absence of a decreased number of hepatic peroxisomes and the presence of VLCFA: (1) pseudo-Zellweger syndrome (deficiency of peroxisomal thiolase activity) and (2) X-linked childhood adrenoleukodystrophy (deficiency of activation of lignoceric acid). Review of the different biochemical defects possible in very-long-chain fatty-acid oxidation reveals different clinical pictures of varying severity, depending on the level at which the biochemical defect occurs.
在本文中，我们报道了两名同胞兄妹，他们的临床表现与新生儿肾上腺脑白质营养不良患者非常相似。与新生儿肾上腺脑白质营养不良患者不同的是，这两名同胞兄妹的肝脏过氧化物酶体体积增大，数量并未减少。极长链脂肪酸（VLCFA）的积累与脂肪酸酰基辅酶A氧化酶的孤立缺乏有关，该酶催化过氧化物酶体β氧化的第一步。血浆中双羟和三羟前列腺烷酸、植烷酸和哌可酸水平正常；此外，在培养的成纤维细胞中还发现酰基辅酶A：磷酸二羟丙酮酰基转移酶活性也正常。将这两名同胞兄妹的临床、生化和细胞化学特征与另外两种疾病的特征进行了比较，这两种疾病的特点是肝脏过氧化物酶体数量未减少且存在VLCFA：（1）假泽尔韦格综合征（过氧化物酶体硫解酶活性缺乏）和（2）X连锁儿童肾上腺脑白质营养不良（二十四烷酸激活缺乏）。对极长链脂肪酸氧化中可能存在的不同生化缺陷进行回顾发现，根据生化缺陷发生的水平不同，会出现不同严重程度的临床症状。
