Barth P G, Gootjes J, Bode H, Vreken P, Majoie C B, Wanders R J
Department of Pediatrics, Emma Children's Hospital/AMC, Amsterdam, The Netherlands.
Neurology. 2001 Dec 11;57(11):1949-55. doi: 10.1212/wnl.57.11.1949.
To report late onset cerebral white matter disease as a distinctive phenotype in peroxisome biogenesis disorder (PBD).
There is phenotypic and genetic overlap among the PBD known as Zellweger syndrome (ZS), infantile Refsum disease (IRD), and neonatal adrenoleukodystrophy (NALD). Distinctive external features are variable among these three disorders, and neurologic deficit has its onset at birth or in infancy. In a structured follow-up cohort of 25 patients with PBD, not including ZS, three patients had an unusual pattern of cerebral white matter disease with onset past the age of 1, not conforming to any of the classic PBD phenotypes.
Clinical phenotyping and follow-up, peroxisomal biochemical determinations in body fluids and fibroblasts, identification of affected PEX gene by genetic complementation in fibroblasts, and MRI studies.
Two unrelated patients with PBD without distinctive external features had normal neurodevelopmental milestones during their first year, followed by rapid deterioration including severe hypotonic pareses, seizures, retinopathy, and deafness. A third patient initially diagnosed with IRD developed cerebral white matter degeneration in the third year of life, complicating the original diagnosis. MRI in all three patients showed cerebral demyelination with sparing of subcortical fibers and pronounced central cerebellar demyelination.
Late-onset cerebral white matter disease may occur in PBD, either following IRD or following normal early development and in the absence of distinctive external features. Peroxisome biogenesis disorder should be included in the differential diagnosis of post-infantile onset of cerebral white matter disease
报告迟发性脑白质病作为过氧化物酶体生物发生障碍（PBD）的一种独特表型。
被称为泽尔韦格综合征（ZS）、婴儿型雷夫叙姆病（IRD）和新生儿肾上腺脑白质营养不良（NALD）的PBD之间存在表型和基因重叠。这三种疾病的独特外部特征各不相同，且神经功能缺损在出生时或婴儿期就已出现。在一个由25名PBD患者（不包括ZS）组成的结构化随访队列中，有三名患者出现了不寻常的脑白质病模式，发病年龄超过1岁，不符合任何经典的PBD表型。
临床表型分析和随访、体液和成纤维细胞中的过氧化物酶体生化测定、通过成纤维细胞中的基因互补鉴定受影响的PEX基因以及MRI研究。
两名无独特外部特征的PBD无关患者在第一年神经发育里程碑正常，随后迅速恶化，包括严重的低张力性轻瘫、癫痫、视网膜病变和耳聋。第三名最初被诊断为IRD的患者在生命的第三年出现脑白质变性，使原诊断复杂化。所有三名患者的MRI均显示脑脱髓鞘，皮质下纤维未受累，小脑中央明显脱髓鞘。
迟发性脑白质病可能发生在PBD中，可继发于IRD之后，或在早期发育正常且无独特外部特征的情况下出现。过氧化物酶体生物发生障碍应纳入婴儿期后发生的脑白质病的鉴别诊断中。
