Hoefler G, Hoefler S, Watkins P A, Chen W W, Moser A, Baldwin V, McGillivary B, Charrow J, Friedman J M, Rutledge L
Kennedy Institute, Baltimore, MD 21205.
J Pediatr. 1988 May;112(5):726-33. doi: 10.1016/s0022-3476(88)80689-9.
Biochemical studies with emphasis on peroxisomal functions were conducted in six patients with well-documented rhizomelic chondrodysplasia punctata (RCDP) and compared with findings in patients with Zellweger syndrome and neonatal adrenoleukodystrophy (ALD). Patients with RCDP had three characteristic biochemical abnormalities: (1) profound defect in plasmalogen (ether lipid) synthesis, which is significantly greater than the analogous defect in Zellweger syndrome or neonatal ALD; (2) reduction of phytanic acid oxidation activity to 1% to 5% of control, similar to that observed in Refsum disease, Zellweger syndrome, and neonatal ALD; (3) presence of the unprocessed form of peroxisomal 3-oxoacyl-coenzyme A thiolase in the postmortem liver of two patients. Other peroxisomal functions were normal, including levels of very long chain fatty acids, pipecolic acid, and bile acid intermediates, and immunoblot studies of peroxisomal acyl-CoA oxidase and bifunctional enzyme in postmortem liver. Unlike what is observed in Zellweger syndrome and neonatal ALD, catalase activity in cultured skin fibroblasts was sedimentable, indicating that peroxisome structure is not grossly deficient in RCDP. The biochemical abnormalities in RCDP were consistent and set it apart from all the other known peroxisomal disorders.
对6例确诊为肢根型点状软骨发育不良（RCDP）的患者进行了重点关注过氧化物酶体功能的生化研究，并与齐韦格综合征和新生儿肾上腺脑白质营养不良（ALD）患者的研究结果进行了比较。RCDP患者有三个特征性的生化异常：（1）缩醛磷脂（醚脂）合成存在严重缺陷，该缺陷明显大于齐韦格综合征或新生儿ALD中的类似缺陷；（2）植烷酸氧化活性降至对照的1%至5%，与雷夫叙姆病、齐韦格综合征和新生儿ALD中观察到的情况相似；（3）两名患者死后肝脏中存在未加工形式的过氧化物酶体3-氧代酰基辅酶A硫解酶。其他过氧化物酶体功能正常，包括极长链脂肪酸、哌可酸和胆汁酸中间体的水平，以及死后肝脏中过氧化物酶体酰基辅酶A氧化酶和双功能酶的免疫印迹研究。与齐韦格综合征和新生儿ALD不同，培养的皮肤成纤维细胞中的过氧化氢酶活性是可沉淀的，这表明RCDP中过氧化物酶体结构没有严重缺陷。RCDP中的生化异常是一致的，使其有别于所有其他已知的过氧化物酶体疾病。
