Clinicopathological and Immunogenetic Characterization in 8 Patients with Familial Hemophagocytic Lymphohistiocytosis Type 2: A Study from North India with Literature Review

Janka GE. Familial and acquired hemophagocytic lymphohistiocytosis. Annu Rev Med. 2012;63:233–46.

Article  CAS  PubMed  Google Scholar 

Janka GE, Lehmberg K. Hemophagocytic syndromes–an update. Blood Rev. 2014;28(4):135–42.

Article  PubMed  Google Scholar 

Shabrish S, Kelkar M, Yadav RM, Bargir UA, Gupta M, Dalvi A, et al. The Spectrum of Clinical, Immunological, and Molecular Findings in Familial Hemophagocytic Lymphohistiocytosis: Experience From India. Front Immunol. 2021;5(12):612583.

Article  Google Scholar 

Rawat A, Arora K, Shandilya J, Vignesh P, Suri D, Kaur G, et al. Flow Cytometry for Diagnosis of Primary Immune Deficiencies—A Tertiary Center Experience From North India. Front Immunol. 2019;11(10):2111.

Article  Google Scholar 

Kogawa K, Lee SM, Villanueva J, Marmer D, Sumegi J, Filipovich AH. Perforin expression in cytotoxic lymphocytes from patients with hemophagocytic lymphohistiocytosis and their family members. Blood. 2002;99(1):61–6.

Article  CAS  PubMed  Google Scholar 

Abdalgani M, Filipovich AH, Choo S, Zhang K, Gifford C, Villanueva J, et al. Accuracy of flow cytometric perforin screening for detecting patients with FHL due to PRF1 mutations. Blood. 2015;126(15):1858–60.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Henter JI, Sieni E, Eriksson J, Bergsten E, Hed Myrberg I, Canna SW, et al. Diagnostic guidelines for familial hemophagocytic lymphohistiocytosis revisited. Blood. 2024;144(22):2308–18.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Rawat A, Sharma M, Vignesh P, Jindal AK, Suri D, Das J, et al. Utility of targeted next generation sequencing for inborn errors of immunity at a tertiary care centre in North India. Sci Rep. 2022;12(1):10416.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, et al. Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. Genet Med. 2015;17(5):405–24.

Article  PubMed  PubMed Central  Google Scholar 

Ishii E, Ueda I, Shirakawa R, Yamamoto K, Horiuchi H, Ohga S, et al. Genetic subtypes of familial hemophagocytic lymphohistiocytosis: correlations with clinical features and cytotoxic T lymphocyte/natural killer cell functions. Blood. 2005;105(9):3442–8.

Article  CAS  PubMed  Google Scholar 

Clementi R, Locatelli F, Dupré L, Garaventa A, Emmi L, Bregni M, et al. A proportion of patients with lymphoma may harbor disease causing variant s of the perforin gene. Blood. 2005;105(11):4424–8.

Article  CAS  PubMed  Google Scholar 

Ueda I, Kurokawa Y, Koike K, Ito S, Sakata A, Matsumora T, et al. Late-onset cases of familial hemophagocytic lymphohistiocytosis with missense perforin gene disease causing variant s. Am J Hematol. 2007;82(6):427–32.

Article  CAS  PubMed  Google Scholar 

Beaty AD, Weller C, Levy B, Vogler C, Ferguson WS, Bicknese A, et al. A teenage boy with late onset hemophagocytic lymphohistiocytosis with predominant neurologic disease and perforin deficiency. Pediatr Blood Cancer. 2008;50(5):1070–2.

Article  PubMed  Google Scholar 

Henter JI, Horne A, Aricó M, Egeler RM, Filipovich AH, Imashuku S, et al. HLH-2004: Diagnostic and therapeutic guidelines for hemophagocytic lymphohistiocytosis. Pediatr Blood Cancer. 2007;48(2):124–31.

Article  PubMed  Google Scholar 

Mhatre S, Madkaikar M, Desai M, Ghosh K. Spectrum of perforin gene disease causing variants in familial hemophagocytic lymphohistiocytosis (FHL) patients in India. Blood Cells Mol Dis. 2015;54(3):250–7.

Article  CAS  PubMed  Google Scholar 

Tesi B, Chiang SCC, El-Ghoneimy D, Hussein AA, Langenskiöld C, Wali R, et al. Spectrum of Atypical Clinical Presentations in Patients with Biallelic PRF1 Missense Disease causing variants. Pediatr Blood Cancer. 2015;62(12):2094–100.

Article  CAS  PubMed  Google Scholar 

Risma KA, Marsh RA. Hemophagocytic Lymphohistiocytosis: Clinical Presentations and Diagnosis. J Allergy Clin Immunol Pract. 2019;7(3):824–32.

Article  PubMed  Google Scholar 

Madkaikar MR, Shabrish S, Kulkarni M, Aluri J, Dalvi A, Kelkar M, et al. Application of Flow Cytometry in Primary Immunodeficiencies: Experience From India. Front Immunol. 2019;10:1248.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Nagai K, Yamamoto K, Fujiwara H, An J, Ochi T, Suemori K, et al. Subtypes of Familial Hemophagocytic Lymphohistiocytosis in Japan Based on Genetic and Functional Analyses of Cytotoxic T Lymphocytes. PLoS ONE. 2010;5(11):e14173.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Zhang K, Jordan MB, Marsh RA, Johnson JA, Kissell D, Meller J, et al. Hypomorphic mutations in PRF1, MUNC13-4, and STXBP2 are associated with adult-onset familial HLH. Blood. 2011;118(22):5794–8.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Lu G, de Xie Z, Ling SK, Hui WR, Kang JY, Yang S, et al. Clinical analysis and follow-up study of Epstein-Barr virus associated-hemophagocytic lymphohistiocytosis in childhood. Zhonghua Er Ke Za Zhi Chin J Pediatr. 2010;48(2):121–6.

Google Scholar 

Wang Y, Wang Z, Zhang J, Wei Q, Tang R, Qi J, et al. Genetic Features of Late Onset Primary Hemophagocytic Lymphohistiocytosis in Adolescence or Adulthood. PLoS ONE. 2014;9(9):e107386.

Article  PubMed  PubMed Central  Google Scholar 

Sun S, Guo X, Zhu Y, Yang X, Li Q, Gao J. Analysis of clinical phenotype and genetic disease causing variant s of a pedigree of familial hemophagocytic lymphohistiocytosis. Zhonghua Yi Xue Yi Chuan Xue Za Zhi Zhonghua Yixue Yichuanxue Zazhi Chin J Med Genet. 2014;31(5):570–3.

CAS  Google Scholar 

Zhang J, Wang YN, Wang JS, Wu L, Wei N, Fu L, et al. The significance of pedigree genetic screening and rapid immunological parameters in the diagnosis of primary hemophagocytic lymphohistiocytosis. Zhonghua Xue Ye Xue Za Zhi Zhonghua Xueyexue Zazhi. 2016;37(7):565–70.

CAS  PubMed  Google Scholar 

Liu C, Li M, Wu X, Yao X, Zhao L. Type 2 familial hemophagocytic lymphohistiocytosis in half brothers. Medicine (Baltimore). 2018;97(30):e11577.

Article  PubMed  Google Scholar 

Mian A, Kumari K, Kaushal S, Fazal F, Kodan P, Batra A, et al. Fatal familial hemophagocytic lymphohistiocytosis with perforin gene (PRF1) disease causing variant and EBV-associated T-cell lymphoproliferative disorder of the thyroid. Autopsy Case Rep. 2019;9(3):e2019101.

Article  Google Scholar 

Ding Q, Guo X, Li Q. Analysis of PRF1gene variant in a child with late-onset familial hemophagocytic lymphohistiocytosis type 2 and severe central nervous system disease. Zhonghua Yi Xue Yi Chuan Xue Za Zhi Zhonghua Yixue Yichuanxue Zazhi Chin J Med Genet. 2019;36(6):592–4.

Google Scholar 

Godby RC, Kraemer RR, May J, Soni S, Reddy V, Thomas JV, et al. Co-Occurrence of Familial Hemophagocytic Lymphohistiocytosis Type 2 and Chronic Active Epstein-Barr Virus in Adulthood. Am J Med Sci. 2021;361(3):388–93.

Article  PubMed  Google Scholar 

Feng W xing, Yang X ying, Li J wei, Gong S, Wu Y, Zhang W hua, et al. Neurologic Manifestations as Initial Clinical Presentation of Familial Hemophagocytic Lymphohistiocytosis Type2 Due to PRF1 Disease causing variant in Chinese Pediatric Patients. Front Genet [Internet]. 2020 Mar 4 [cited 2024 Jul 7];11. Available from: https://www.frontiersin.org/journals/genetics/articles/https://doi.org/10.3389/fgene.2020.00126/full

Shi Y, Qiao Z, Bi X, Zhang C, Fu J, Jia Y, et al. RF1 Gene Disease causing variant in Familial Hemophagocytic Lymphohistiocytosis 2: A Family Report and Literature Review. Pharmacogenomics Pers Med. 2021;16(14):1637–45.

Google Scholar 

Gadoury-Levesque V, Dong L, Su R, Chen J, Zhang K, Risma KA, et al. Frequency and spectrum of disease-causing variants in 1892 patients with suspected genetic HLH disorders. Blood Adv. 2020;4(12):2578–94.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Jin Z, Wang Y, Wang J, Zhang J, Wu L, Gao Z, et al. Primary hemophagocytic lymphohistiocytosis in adults: the utility of family surveys in a single-center study from China. Orphanet J Rare Dis. 2018;13(1):17.

Article  PubMed  PubMed Central  Google Scholar 

Hu LY, Wan L, Wang QH, Shi XY, Meng Y, Yang XF, et al. Case Report: Chronic inflammatory demyelinating polyradiculoneuropathy rather than hemophagocytic lymphohistiocytosis-the initial phenotype of PRF1 gene disease causing variant. Front Immunol. 2023;14:1306338.

Article  CAS  PubMed 

Comments (0)

No login
gif