Mandel Hanna, Korman Stanley H
Metabolic Disease Unit, Department of Pediatrics, Rambam Medical Center, Technion-Israel Institute of Technology, Bruce Rappaport Faculty of Medicine, Haifa, Israel.
Adv Exp Med Biol. 2003;544:9-30. doi: 10.1007/978-1-4419-9072-3_2.
Peroxisomes perform a multitude of biosynthetic and catabolic functions, many of which are related to lipid metabolism. Peroxisomal disorders result either from deficiency of a single peroxisomal enzyme or protein, or from a defect in the complex mechanism of peroxisomal biogenesis, resulting in deficiency of several or multiple peroxisomal functions. These can be assessed by a battery of biochemical assays, enabling a biochemical phenotype to be defined that is specific and diagnostic for each of the peroxisomal disorders. Some peroxisomal disorders have unique and specific clinical phenotypes, which may be diagnostic. Others share patterns of clinical abnormalities (particularly neurological dysfunction, craniofacial dysmorphism, skeletal defects, sensory deafness, retinopathy) consistent with defined clinical phenotypes, but with considerable overlap and heterogeneity. To a certain extent, the clinical features of a particular disorder reflect the accumulation or deficiency of specific metabolites. Thus, the same clinical phenotypes may be caused by both single enzyme defects and PBDs. Furthermore, the same defect may present with different clinical phenotypes. In general, the severity of the clinical phenotype correlates with the degree of biochemical dysfunction. The clinical heterogeneity of peroxisomal disorders constitutes a diagnostic challenge demanding a high index of suspicion on the clinician's part.
过氧化物酶体执行多种生物合成和分解代谢功能，其中许多与脂质代谢有关。过氧化物酶体疾病要么源于单一过氧化物酶体酶或蛋白质的缺乏，要么源于过氧化物酶体生物发生的复杂机制缺陷，导致几种或多种过氧化物酶体功能缺乏。这些可以通过一系列生化检测来评估，从而能够定义一种生化表型，该表型对于每种过氧化物酶体疾病都是特异的且具有诊断性。一些过氧化物酶体疾病具有独特而特异的临床表型，可能具有诊断价值。其他疾病则具有与已定义临床表型一致的临床异常模式（特别是神经功能障碍、颅面部畸形、骨骼缺陷、感觉性耳聋、视网膜病变），但存在相当大的重叠和异质性。在一定程度上，特定疾病的临床特征反映了特定代谢物的积累或缺乏。因此，相同的临床表型可能由单酶缺陷和过氧化物酶体生物合成障碍（PBDs）共同导致。此外，相同的缺陷可能表现出不同的临床表型。一般来说，临床表型的严重程度与生化功能障碍的程度相关。过氧化物酶体疾病的临床异质性对诊断构成了挑战，需要临床医生保持高度的怀疑指数。
