Division of Pediatric Hematology/Oncology, Department of Pediatrics, C.S. Mott Children's Hospital, University of Michigan, Ann Arbor, Mich.
Division of Immunology and Allergy, Department of Pediatrics, Hospital for Sick Children, University of Toronto, Toronto, ON, Canada.
J Allergy Clin Immunol Pract. 2022 Jul;10(7):1714-1722. doi: 10.1016/j.jaip.2022.04.004. Epub 2022 Apr 22.
Given the ubiquity of leukopenia and sinopulmonary infections in childhood, differentiating patients with inborn errors of immunity (IEI) from otherwise healthy patients can be challenging. The diagnostic complexity is further exacerbated in disorders with wide phenotypic variability such as warts, hypogammaglobulinemia, infections, and myelokathexis (WHIM) syndrome. However, using a Sherlock approach with careful attention to details in the patient's medical history and physical examination coupled with a comprehensive family history can heighten the index of suspicion for underlying IEI. Subsequent iterative and deductive reasoning incorporating results from laboratory interrogation, response (or lack thereof) to standard therapy, and emergence of new symptoms can further aid in a timely diagnosis of IEI. Herein, we detail a WHIM syndrome kindred with marked phenotype variability, identified after the presentation of a child with intermittent neutropenia and sinopulmonary infections. The complexity of this kindred highlights the utility of an interspecialty, collaborative Sherlock approach to diagnosis, and care. In addition, the genetic underpinnings, diagnostic approaches, clinical features, supportive care options, and management of WHIM syndrome are reviewed.
鉴于儿童时期白细胞减少症和鼻肺感染的普遍性，将免疫固有缺陷（IEI）患者与其他健康患者区分开来可能具有挑战性。在具有广泛表型变异性的疾病中，如疣、低丙种球蛋白血症、感染和骨髓空洞症（WHIM）综合征，诊断的复杂性进一步加剧。然而，使用 Sherlock 方法，仔细注意患者病史和体格检查中的细节，以及全面的家族史，可以提高对潜在 IEI 的怀疑指数。随后，通过实验室检查结果、对标准治疗的反应（或缺乏反应）以及新症状的出现进行迭代和演绎推理，可以帮助及时诊断 IEI。在此，我们详细描述了一个 WHIM 综合征家族，该家族具有明显的表型变异性，在一名间歇性中性粒细胞减少症和鼻肺感染患儿出现后被发现。该家族的复杂性突出了跨专业、协作 Sherlock 方法在诊断和治疗中的实用性。此外，还回顾了 WHIM 综合征的遗传基础、诊断方法、临床特征、支持性护理选择以及管理。
