Rare cause of Hemophagocytic Lymphohistiocytosis due to mutation in PRF1 and SH2D1A genes in two children – a case report with a review

Sheth, Jayesh; Patel, Akash J.; Shah, Raju; Bhavsar, Riddhi; Trivedi, Sunil; Sheth, Frenny

doi:10.1186/s12887-019-1444-4

Cited by 7 publications

(7 citation statements)

References 30 publications

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“…The missense mutations (c.445G>A) are common in Spanish patients while in Japanese patients with HLH, the most common mutation is c.1090_1091delCT (accounting for approximately 62.5% of the PRF1 mutations), followed by c.207delC (about 37.5% of PRF1 mutations). 15 , 16 …”

Section: Discussionmentioning

confidence: 99%

RF1 Gene Mutation in Familial Hemophagocytic Lymphohistiocytosis 2: A Family Report and Literature Review

Shi¹,

Qiao²,

Bi³

et al. 2021

PGPM

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Objective Gene mutation analysis was performed on a family with familial hemophagocytic lymphohistiocytosis (FHL) so as to provide an accurate etiological diagnosis, leading to genetic counseling for the family members. Methods The clinical data of two probands (siblings) with FHL in one family were analyzed, and eight genes related to the onset of the primary hemophagocytic lymphohistiocytosis (pHLH) ( PRF1, UNC13D, STX11, STXBP2, SH2D1A, BIRC4/XIAP, Rab27a, LYST ) were detected and analyzed in the probands and their parents with whole exome sequencing. Results Proband 1 was a two-year-old male with the clinical manifestations of fever, hepatosplenomegaly, and a decreased peripheral blood cell count, sCD25: 12504pg/mL. The results of genetic testing showed that there was a c.1349C>T heterozygous missense mutation and a c.853_855del heterozygous mutation in the PRF1 in proband 1. Proband 2 was an eight-year-old female with the clinical manifestations of convulsions and disturbance of consciousness with fever. The genetic test results were the same as those of proband 1. There was a single heterozygous mutation in the parents of the probands, and both probands had compound heterozygous mutations. Conclusion According to the clinical manifestations, laboratory tests, and results of the family molecular genetic testing, the probands could be clinically diagnosed as FHL2. The results of gene sequencing revealed that this was an autosomal recessive family with familial hemophagocytic syndrome. A rare pathogenic mutation (c.853_855del) in the PRF1 was discovered in the two patients with HLH.

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Section: Discussionmentioning

confidence: 99%

RF1 Gene Mutation in Familial Hemophagocytic Lymphohistiocytosis 2: A Family Report and Literature Review

Shi¹,

Qiao²,

Bi³

et al. 2021

PGPM

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“…Other mutations in genes associated with the development of MAS may be broadly categorised as those involved in antiviral defences, the regulation of inflammasome activity, other immune response pathways and overall regulation of metabolism [212]. This is unsurprising given that bi-allelic mutations in syntaxin binding protein 2 (STXBP2), syntaxin11 (STX11), PRF1, UNC13D and other genes regulating and enabling the clearance of peripheral blood mononuclear cells (PBMCs) by CD8+ T lymphocytes and NK cells are the cause of familial hemophagocytic lymphohistiocytosis (FHL) [213,214]. In this illness, the impaired capacity to lyse antigen presenting cells (APCs) and T cells compromises the clearance of pathogen-infected cells and prolonged antigen stimulation of T cells leads to chronic macrophage activation and massive release of proinflammatory chemokines and cytokines [215,216,189,191,217].…”

Section: Factors Involved In the Pathophysiology Of Masmentioning

confidence: 99%

The cytokine storms of COVID-19, H1N1 influenza, CRS and MAS compared. Can one sized treatment fit all?

Morris

Bortolasci

Puri³

et al. 2021

Cytokine

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An analysis of published data appertaining to the cytokine storms of COVID-19, H1N1 influenza, cytokine release syndrome (CRS), and macrophage activation syndrome (MAS) reveals many common immunological and biochemical abnormalities. These include evidence of a hyperactive coagulation system with elevated D-dimer and ferritin levels, disseminated intravascular coagulopathy (DIC) and microthrombi coupled with an activated and highly permeable vascular endothelium. Common immune abnormalities include progressive hypercytokinemia with elevated levels of TNF-α, interleukin (IL)-6, and IL-1β, proinflammatory chemokines, activated macrophages and increased levels of nuclear factor kappa beta (NFκB). Inflammasome activation and release of damage associated molecular patterns (DAMPs) is common to COVID-19, H1N1, and MAS but does not appear to be a feature of CRS. Elevated levels of IL-18 are detected in patients with COVID-19 and MAS but have not been reported in patients with H1N1 influenza and CRS. Elevated interferon-γ is common to H1N1, MAS, and CRS but levels of this molecule appear to be depressed in patients with COVID-19. CD4+ T, CD8+ and NK lymphocytes are involved in the pathophysiology of CRS, MAS, and possibly H1N1 but are reduced in number and dysfunctional in COVID-19. Additional elements underpinning the pathophysiology of cytokine storms include Inflammasome activity and DAMPs. Treatment with anakinra may theoretically offer an avenue to positively manipulate the range of biochemical and immune abnormalities reported in COVID-19 and thought to underpin the pathophysiology of cytokine storms beyond those manipulated via the use of, canakinumab, Jak inhibitors or tocilizumab. Thus, despite the relative success of tocilizumab in reducing mortality in COVID-19 patients already on dexamethasone and promising results with Baricitinib, the combination of anakinra in combination with dexamethasone offers the theoretical prospect of further improvements in patient survival. However, there is currently an absence of trial of evidence in favour or contravening this proposition. Accordingly, a large well powered blinded prospective randomised controlled trial (RCT) to test this hypothesis is recommended.

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“…La forma primaria (FHL hereditaria) o genética es un trastorno de carácter autosómico recesivo, su incidencia étnica a nivel mundial aún no está clara sin embargo se observa con mayor frecuencia en familias consanguíneas (14). La Linfohistiocitosis hemofagocítica hereditaria se ha subclasificado en 5 tipos: FHL 1 a FHL 5 (15) , estos…”

Section: Linfohistiocitosis Hemofagocítica Primaria (Fhl) O Genéticaunclassified

Linfohistiocitosis Hemofagocítica (HLH) en pediatría; nuevas opciones terapéuticas.

Cruz¹,

Borja²

2022

TEJOM

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Resumen Introducción: La Linfohistiocitosis hemofagocítica (HLH) es una patología con alta tasa de mortalidad, que se caracteriza por presentar una clínica variable con rápido progreso a fallo multiorgánico sin una incidencia clara reportada a nivel de Latinoamérica, probablemente por la falta de sospecha diagnóstica, su desencadenante ocasiona una respuesta inmune exagerada con tormenta de citocinas responsables del cuadro clínico. Actualmente se maneja el tratamiento conforme a lo establecido en el protocolo HLH 1994- 2004, no obstante nuevas investigaciones en la última década se han realizado con agentes terapéuticos menos agresivos. Objetivo: Actualizar la literatura y nuevas opciones terapéuticas sobre la Linfohistiocitosis hemofagocitica. Metodología: Se realizó una búsqueda bibliográfica en base de datos como: PUBMED, MEDLINE, COCHRANE, se obtuvo artículos de revistas médicas como: THE JOURNAL OF INMUNOLOGY, BMC PEDIATRICS, PEDIATRIC RHEUMATOLOGY, JOURNAL OF MEDICAL, BMC INFECTIOUS DISEASES etc. Resultados: La terapia establecida por la Histiocyte Society en el estudio HLH-2004 se mantiene como la terapia estándar para la Linfohistiocitosis Hemofagocítica, si se confirma la co-infección por virus de Epstein Barr el anticuerpo monoclonal CD20 -Rituximab debe ser iniciado, la terapia inmunomoduladora presentó resultados favorables, no obstante faltan estudios en poblaciones más grandes para establecer su uso como terapia inicial, sin embargo se podría utilizar como terapia coadyuvante. Conclusiones: La Linfohistiocitosis Hemofagocítica es una patología con alta tasa de mortalidad, la sospecha diagnóstica e inicio temprano del tratamiento mejora la tasa de supervivencia.

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Rare cause of Hemophagocytic Lymphohistiocytosis due to mutation in PRF1 and SH2D1A genes in two children – a case report with a review

Cited by 7 publications

References 30 publications

RF1 Gene Mutation in Familial Hemophagocytic Lymphohistiocytosis 2: A Family Report and Literature Review

RF1 Gene Mutation in Familial Hemophagocytic Lymphohistiocytosis 2: A Family Report and Literature Review

The cytokine storms of COVID-19, H1N1 influenza, CRS and MAS compared. Can one sized treatment fit all?

Linfohistiocitosis Hemofagocítica (HLH) en pediatría; nuevas opciones terapéuticas.

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