Zellweger spectrum disorders (ZSD) constitute a group of rare autosomal recessive disorders characterized by a defect in peroxisome biogenesis due to mutations in one of 13 PEX genes. The broad clinical heterogeneity especially in late-onset presenting patients and a mild phenotype complicates and delays the diagnostic process. Here, we report a case of mild ZSD, due to novel PEX1 variants. The patient presented with an early hearing loss, bilateral cataracts, and leukodystrophy on magnetic resonance (MR) images. Normal results of serum very-long-chain fatty acids (VLCFA) and phytanic acid were found. Molecular diagnostics were performed to uncover the etiology of the clinical phenotype. Using whole exome sequencing, there have been found two variants in the PEX1 gene—c.3450T>A (p.Cys1150*) and c.1769T>C (p.Leu590Pro). VLCFA measurement in skin fibroblasts and C26:0-lysoPC in dried blood spot therefore was performed. Both results were in line with the diagnosis of ZSD. To conclude, normal results of routine serum VLCFA and branched-chain fatty acid measurement do not exclude mild forms of ZSD. The investigation of C26:0-lysoPC should be included in the diagnostic work-up in patients with cataract, hearing loss, and leukodystrophy on MR images suspected to suffer from ZSD.

中文翻译：

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由于功能确认的新型PEX1变异，导致轻度Zellweger综合征。

Zellweger谱系疾病（ZSD）构成了一组罕见的常染色体隐性遗传疾病，其特征是由于13个PEX基因之一的突变导致过氧化物酶体生物发生缺陷。广泛的临床异质性，尤其是在晚期发病的患者和轻度的表型，使诊断过程复杂化并延迟了诊断过程。在这里，我们报告了由于新型PEX1变体导致的轻度ZSD病例。该患者在磁共振（MR）图像上出现早期听力下降，双侧白内障和白细胞营养不良。发现血清超长链脂肪酸（VLCFA）和植酸的正常结果。进行分子诊断以揭示临床表型的病因。使用整个外显子组测序，在PEX1中发现了两个变体基因-c.3450T> A（p.Cys1150 *）和c.1769T> C（p.Leu590Pro）。因此，进行了皮肤成纤维细胞和干血斑中C26：0-lysoPC的VLCFA测量。两项结果均符合ZSD的诊断。总之，常规血清VLCFA和支链脂肪酸测量的正常结果并不排除ZSD的轻度形式。对于怀疑患有ZSD的MR图像，白内障，听力损失和白细胞营养不良的患者，应在诊断检查中包括C26：0-lysoPC的检查。