A previously healthy 19-year-old Syrian man presented with atypical and severe mucosal leishmaniasis caused by Leishmania tropica. During a 2-year period, he had three severe relapses despite various treatment strategies, including liposomal amphotericin B and Miltefosine. Because of the unusual clinical presentation, potential underlying immunodeficiency was investigated. Normal T and NK cell counts were found. The B cell count was slightly elevated at 0.7 × 10⁹ cells/L (0.09 × 10⁹ to 0.57 × 10⁹ cells/L), but the proportions of memory and isotype switched memory B cells were severely diminished IgG levels were low, at 309 mg/dL (610–1490 mg/dL). The initial IgM and IgA levels were within normal range, but the IgA levels decreased to 57 mg/dL (70–430 mg/dL) during follow up. Common variable immunodeficiency (CVID) was initially suspected, because the immunological results of low IgG and IgA, low switched memory B cells, no profound T cell deficiency found and absence of secondary cause of hypogammaglobulinemia were compatible with this diagnosis (ESID 2019). However, the highly unusual and severe clinical presentation of L. tropica is not suggestive of B-cell deficiency or CVID. Eventually a pathogenic nonsense variant in the CD40 ligand gene [p.(Arg11^∗)] was identified by whole genome sequencing, thus enabling the diagnosis of X-linked hyper IgM syndrome. This case illustrates and supports the potential for the use of whole genome sequencing in accurate diagnosis of primary immunodeficiencies.

一名原本健康的 19 岁叙利亚男子患有由热带利什曼原虫引起的非典型严重粘膜利什曼病。尽管采用了脂质体两性霉素 B 和米替福辛等多种治疗策略，但在 2 年期间，他还是出现了 3 次严重复发。由于临床表现不寻常，因此对潜在的免疫缺陷进行了调查。发现 T 细胞和 NK 细胞计数正常。 B 细胞计数略有升高，为 0.7 × 10 ^{9 个}细胞/L（0.09 × 10 ⁹至 0.57 × 10 ^{9 个}细胞/L），但记忆和同型转换记忆 B 细胞的比例严重减少，IgG 水平较低，为309 毫克/分升（610–1490 毫克/分升）。初始 IgM 和 IgA 水平在正常范围内，但随访期间 IgA 水平降至 57 mg/dL (70–430 mg/dL)。最初怀疑是常见变异型免疫缺陷 (CVID)，因为 IgG 和 IgA 低、记忆 B 细胞转换低、未发现严重 T 细胞缺陷以及不存在低丙种球蛋白血症继发原因的免疫学结果与该诊断相符 (ESID 2019)。然而，热带李斯特菌极不寻常且严重的临床表现并不提示 B 细胞缺陷或 CVID。最终，通过全基因组测序鉴定出 CD40 配体基因 [p.(Arg11 ^* )] 中的致病性无义变异，从而能够诊断 X 连锁高 IgM 综合征。该案例说明并支持了使用全基因组测序准确诊断原发性免疫缺陷的潜力。