NEMO-NDAS: A Panniculitis in the Young Representing an Autoinflammatory Disorder in Disguise.
NEMO-NDAS: A Panniculitis in the Young Representing an Autoinflammatory Disorder in Disguise.
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DOI：
10.1097/dad.0000000000002144
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发表时间：
2022-06-01
影响因子：
1.1
通讯作者：
Salgado, Claudia M.
中科院分区：
文献类型：
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作者：
Hegazy, Shaymaa;Marques, Mariana C.;Canna, Scott W.;Goldbach-Mansky, Raphaela;de Jesus, Adriana A.;Reyes-Mugica, Miguel;Salgado, Claudia M.
15个月大的非洲裔足月男性，无症状镰状细胞特征，自2周龄以来出现一过性红斑性皮下结节，累及除面部外的全身。皮肤病变发展为脂肪萎缩和色素沉着。2个月大时在不同科室进行的最初皮肤活检，最初被误诊为新生儿皮下脂肪坏死，尽管缺乏典型的放射性晶体和针状裂隙。4个月大时，他出现全身性炎症表现，包括发烧、新发皮疹、明显的眶周水肿和发育不全。广泛的检查显示白细胞增多、高钙血症、炎症标志物升高、高甘油三酯血症和转氨炎。眼睑的新皮肤活检被诊断为中性粒细胞小叶泛膜炎伴坏死脂肪细胞。最初的全外显子组测序未发现任何致病突变，但基于额外的临床病理数据，要求对自身炎症性疾病进行WES再分析，并发现IKBKG c. 671+3G> c的嵌合体内含子突变。该突变编码一个缺失外显子5的mRNA，导致NEMO Δ-exon 5自身炎症综合征（NDAS）。NEMO-NDAS是一种全身性自身炎症性疾病（said），可能在幼儿中表现为不明原因的全身膜炎，应监测其免疫缺陷和/或自身炎症性疾病。在这种情况下，应考虑在调查中使用全基因组/外显子组测序来鉴别诊断自身炎症性疾病。Kappa-B激酶调控亚基γ抑制剂（IKBKG）位于染色体Xq28上，编码NF-κB必需调节剂（NEMO），这是NF- kb激活的上游关键分子。
A 15 - month-old full-term male of African descent with an asymptomatic sickle cell trait, presented with episodes of transient erythematous subcutaneous nodules involving the entire body except the face, since 2 weeks of age. The skin lesions evolved to areas of lipoatrophy and hyperpigmentation. An initial skin biopsy, studied at a different Department at 2 months of age, was initially misinterpreted as subcutaneous fat necrosis of the newborn despite the lack of the typical radiated crystals and needle-shaped clefts characterizing that entity. At 4 months of age, he developed systemic inflammatory manifestations including fever, a new rash, significant periorbital edema, and failure to thrive. An extensive workup showed leukocytosis, hypercalcemia, elevated inflammatory markers, hypertriglyceridemia, and transaminitis. A new skin biopsy of the eyelid was diagnosed as neutrophilic lobular panniculitis with necrotic adipocytes. An initial whole-exome sequencing did not identify any causative mutations, but a WES reanalysis focused on autoinflammatory disorders was requested based on additional clinicopathologic data, and revealed a mosaic intronic mutation in IKBKG c. 671+3G>C. This mutation encodes an mRNA missing exon 5 resulting in NEMO Δ-exon 5 Autoinflammatory Syndrome (NDAS). NEMO-NDAS is one of the systemic autoinflammatory diseases (SAIDs) that may appear as an unexplained panniculitis in young children, who should be monitored for immunodeficiency and/or autoinflammatory disease. The differential diagnosis of autoinflammatory disorders should be considered in such cases incorporating the use of the whole genome/ exome sequencing in the investigation. The Inhibitor of Kappa-B Kinase Regulatory Subunit Gamma (IKBKG) is located on chromosome Xq28 and encodes the NF-κB essential modulator (NEMO), a critical molecule upstream of NF-kB activation.