PDF(Pubmed)
Abstract：
Sphingosine phosphate lyase insufficiency syndrome (SPLIS) is associated with biallelic variants in SGPL1, comprising a multisystemic disease characterized by steroid resistant nephrotic syndrome, primary adrenal insufficiency, neurological problems, skin abnormalities and immunodeficiency in described cases. Signal transducer and activator of transcription 1 (STAT1) plays an important role in orchestrating an appropriate immune response through JAK-STAT pathway. Biallelic STAT1 loss of function (LOF) variants lead to STAT1 deficiency with a severe phenotype of immunodeficiency with increased frequency of infections and poor outcome if untreated.
We report novel homozygous SGPL1 and STAT1 variants in a newborn of Gambian ethnicity with clinical features of SPLIS and severe combined immunodeficiency. The patient presented early in life with nephrotic syndrome, severe respiratory infection requiring ventilation, ichthyosis, and hearing loss, with T-cell lymphopenia. The combination of these two conditions led to severe combined immunodeficiency with inability to clear respiratory tract infections of viral, fungal, and bacterial nature, as well as severe nephrotic syndrome. The child sadly died at 6 weeks of age despite targeted treatments.
We report the finding of two novel, homozygous variants in SGPL1 and STAT1 in a patient with a severe clinical phenotype and fatal outcome early in life. This case highlights the importance of completing the primary immunodeficiency genetic panel in full to avoid missing a second diagnosis in other patients presenting with similar severe clinical phenotype early in life. For SPLIS no curative treatment is available and more research is needed to investigate different treatment modalities. Hematopoietic stem cell transplantation (HSCT) shows promising results in patients with autosomal recessive STAT1 deficiency. For this patient\'s family, identification of the dual diagnosis has important implications for future family planning. In addition, future siblings with the familial STAT1 variant can be offered curative treatment with HSCT.
We report novel homozygous SGPL1 and STAT1 variants in a newborn of Gambian ethnicity with clinical features of SPLIS and severe combined immunodeficiency. The patient presented early in life with nephrotic syndrome, severe respiratory infection requiring ventilation, ichthyosis, and hearing loss, with T-cell lymphopenia. The combination of these two conditions led to severe combined immunodeficiency with inability to clear respiratory tract infections of viral, fungal, and bacterial nature, as well as severe nephrotic syndrome. The child sadly died at 6 weeks of age despite targeted treatments.
We report the finding of two novel, homozygous variants in SGPL1 and STAT1 in a patient with a severe clinical phenotype and fatal outcome early in life. This case highlights the importance of completing the primary immunodeficiency genetic panel in full to avoid missing a second diagnosis in other patients presenting with similar severe clinical phenotype early in life. For SPLIS no curative treatment is available and more research is needed to investigate different treatment modalities. Hematopoietic stem cell transplantation (HSCT) shows promising results in patients with autosomal recessive STAT1 deficiency. For this patient\'s family, identification of the dual diagnosis has important implications for future family planning. In addition, future siblings with the familial STAT1 variant can be offered curative treatment with HSCT.
摘要：
■磷酸鞘氨醇裂解酶功能不全综合征（SPLIS）与SGPL1中的双等位基因变异有关，包括一种以类固醇耐药性肾病综合征为特征的多系统疾病，原发性肾上腺功能不全,神经问题,描述病例中的皮肤异常和免疫缺陷。信号转导和转录激活因子1（STAT1）在通过JAK-STAT途径协调适当的免疫应答中起着重要作用。双等位基因STAT1功能丧失（LOF）变体导致STAT1缺乏，具有严重的免疫缺陷表型，感染频率增加，如果不治疗，结果较差。
■我们报道了一个冈比亚种族新生儿的新型纯合SGPL1和STAT1变异体，具有SPLIS和严重联合免疫缺陷的临床特征。病人早期出现肾病综合征,需要通气的严重呼吸道感染，鱼鳞病,听力损失,T细胞淋巴细胞减少症.这两种情况的结合导致严重的联合免疫缺陷，无法清除呼吸道感染的病毒，真菌,和细菌的性质，以及严重的肾病综合征.尽管有针对性的治疗，孩子在6周大的时候不幸死亡。
■我们报告了两部小说的发现，SGPL1和STAT1中的纯合变体在具有严重临床表型和生命早期致命结果的患者中。该病例强调了完整完成原发性免疫缺陷遗传小组的重要性，以避免在生命早期表现出类似严重临床表型的其他患者中错过第二次诊断。对于SPLIS没有治愈性治疗，需要更多的研究来研究不同的治疗方式。造血干细胞移植（HSCT）在常染色体隐性遗传STAT1缺乏症患者中显示出有希望的结果。对于这个病人的家人来说，双重诊断的识别对未来的计划生育具有重要意义。此外,未来患有家族性STAT1变异体的兄弟姐妹可以接受HSCT治疗.
■我们报道了一个冈比亚种族新生儿的新型纯合SGPL1和STAT1变异体，具有SPLIS和严重联合免疫缺陷的临床特征。病人早期出现肾病综合征,需要通气的严重呼吸道感染，鱼鳞病,听力损失,T细胞淋巴细胞减少症.这两种情况的结合导致严重的联合免疫缺陷，无法清除呼吸道感染的病毒，真菌,和细菌的性质，以及严重的肾病综合征.尽管有针对性的治疗，孩子在6周大的时候不幸死亡。
■我们报告了两部小说的发现，SGPL1和STAT1中的纯合变体在具有严重临床表型和生命早期致命结果的患者中。该病例强调了完整完成原发性免疫缺陷遗传小组的重要性，以避免在生命早期表现出类似严重临床表型的其他患者中错过第二次诊断。对于SPLIS没有治愈性治疗，需要更多的研究来研究不同的治疗方式。造血干细胞移植（HSCT）在常染色体隐性遗传STAT1缺乏症患者中显示出有希望的结果。对于这个病人的家人来说，双重诊断的识别对未来的计划生育具有重要意义。此外,未来患有家族性STAT1变异体的兄弟姐妹可以接受HSCT治疗.
