Fazi C, Lodi L, Magi L, Canessa C, Giovannini M, Pelosi C, Pochiero F, Procopio E, Donati M A, Azzari C, Ricci S
Pediatric Immunology Division, Meyer Children's Hospital, Florence, Italy.
Department of Health Sciences, University of Florence, Florence, Italy.
Front Pediatr. 2022 Mar 25;10:852943. doi: 10.3389/fped.2022.852943. eCollection 2022.
Zellweger syndrome (ZS) is a congenital autosomal recessive disease within the spectrum of peroxisome biogenesis disorders, characterized by the impairment of peroxisome assembly. The presence of peroxisome enzyme deficiencies leads to complex developmental sequelae, progressive disabilities, and multiorgan damage, due to intracellular accumulation of very-long-chain fatty acids (VLCFAs).
We report the case of an infant affected by ZS in which agammaglobulinemia, detected through neonatal screening of congenital immunodeficiencies, appeared as a peculiar trait standing out among all the other classical characteristics of the syndrome. The exome analysis through next-generation sequencing (NGS), which had previously confirmed the diagnostic suspicion of ZS, was repeated, but no mutations causative of inborn error of immunity (humoral defect) were detected.
In this case, no genetic variants accountable for the abovementioned agammaglobulinemia were detected. Given that the scientific literature reports the involvement of peroxisomes in the activation of Nuclear Factor κ-light-chain-enhancer of activated B cells (NF-κB) pathway, which is crucial for B-cell survival, with this work, we hypothesize the existence of a link between ZS and humoral immunodeficiencies. Further studies are required to confirm this hypothesis.
泽尔韦格综合征（ZS）是一种先天性常染色体隐性疾病，属于过氧化物酶体生物发生障碍谱系，其特征为过氧化物酶体组装受损。由于超长链脂肪酸（VLCFA）在细胞内蓄积，过氧化物酶体酶缺乏会导致复杂的发育后遗症、进行性残疾和多器官损害。
我们报告了一例受ZS影响的婴儿病例，通过先天性免疫缺陷新生儿筛查检测到的无丙种球蛋白血症，在该综合征的所有其他典型特征中表现为一个独特的特征。通过新一代测序（NGS）进行的外显子组分析之前已证实对ZS的诊断怀疑，此次重复检测，但未检测到导致先天性免疫缺陷（体液缺陷）的突变。
在本病例中，未检测到可解释上述无丙种球蛋白血症的基因变异。鉴于科学文献报道过氧化物酶体参与激活B细胞活化核因子κB（NF-κB）途径，这对B细胞存活至关重要，通过本研究，我们推测ZS与体液免疫缺陷之间存在联系。需要进一步研究来证实这一假设。
