Pub Date : 2022-12-01DOI: 10.14785/lymphosign-2022-0013
Laura Abrego Fuentes, Irene Chair, P. Vadas, C. Roifman
Background: Autoinflammatory diseases are a genetically heterogeneous group of conditions characterized by excessive activation of the innate immune system. They frequently present with overlapping features, particularly in cases of digenic or polygenic inheritance. The most common cause of autoinflammation arises from causative variants in the MEFV gene, responsible for familial Mediterranean fever. Clinical features include recurrent episodes of fever with serositis and amyloidosis. Individuals with variants in MEFV that present atypically with heterogeneous autoinflammatory features have also been described. Notably, gene modifiers of MEFV, such as NOD2 encoding an intracellular bacterial sensor, can result in more severe disease. NOD2 underlies a number of autoinflammatory and immunodeficiency conditions, including Blau syndrome. To date, Blau syndrome has not been described in the context of MEFV. Aim: To expand the presentation and phenotype of autoinflammatory disease associated with defects in the NOD2 and MEFV genes. Methods: A retrospective review of the patient’s chart was performed, including family history, medical history, immune laboratory evaluation, and genetics. Results: We describe here a 68-year-old male with a remarkable medical history since childhood of skin rash, erythroderma, recurrent infections, autoinflammation, arthritis, uveitis, and malignancy. A significant family history of cancer and autoinflammation was noted. Genetic work-up involving a 17-gene autoinflammatory panel revealed 3 heterozygous variants of uncertain significance, 2 of which were present in the MEFV gene and one in the NOD2 gene. His features were consistent with an overlapping phenotype of Blau syndrome and atypical FMF. Conclusion: Heterozygous variants in NOD2 and MEFV can result in a spectrum of autoinflammatory disorders with a heterogeneous phenotype. The NOD2 variant identified in our patient has not previously been associated with Blau syndrome. Statement of Novelty: We describe a patient harbouring heterozygous mutations in the MEFV and NOD2 genes marked by recurrent childhood infections.
{"title":"Heterogeneous phenotype of autoinflammatory disease in a patient with mutations in NOD2 and MEFV genes","authors":"Laura Abrego Fuentes, Irene Chair, P. Vadas, C. Roifman","doi":"10.14785/lymphosign-2022-0013","DOIUrl":"https://doi.org/10.14785/lymphosign-2022-0013","url":null,"abstract":"Background: Autoinflammatory diseases are a genetically heterogeneous group of conditions characterized by excessive activation of the innate immune system. They frequently present with overlapping features, particularly in cases of digenic or polygenic inheritance. The most common cause of autoinflammation arises from causative variants in the MEFV gene, responsible for familial Mediterranean fever. Clinical features include recurrent episodes of fever with serositis and amyloidosis. Individuals with variants in MEFV that present atypically with heterogeneous autoinflammatory features have also been described. Notably, gene modifiers of MEFV, such as NOD2 encoding an intracellular bacterial sensor, can result in more severe disease. NOD2 underlies a number of autoinflammatory and immunodeficiency conditions, including Blau syndrome. To date, Blau syndrome has not been described in the context of MEFV. Aim: To expand the presentation and phenotype of autoinflammatory disease associated with defects in the NOD2 and MEFV genes. Methods: A retrospective review of the patient’s chart was performed, including family history, medical history, immune laboratory evaluation, and genetics. Results: We describe here a 68-year-old male with a remarkable medical history since childhood of skin rash, erythroderma, recurrent infections, autoinflammation, arthritis, uveitis, and malignancy. A significant family history of cancer and autoinflammation was noted. Genetic work-up involving a 17-gene autoinflammatory panel revealed 3 heterozygous variants of uncertain significance, 2 of which were present in the MEFV gene and one in the NOD2 gene. His features were consistent with an overlapping phenotype of Blau syndrome and atypical FMF. Conclusion: Heterozygous variants in NOD2 and MEFV can result in a spectrum of autoinflammatory disorders with a heterogeneous phenotype. The NOD2 variant identified in our patient has not previously been associated with Blau syndrome. Statement of Novelty: We describe a patient harbouring heterozygous mutations in the MEFV and NOD2 genes marked by recurrent childhood infections.","PeriodicalId":53881,"journal":{"name":"LymphoSign Journal-The Journal of Inherited Immune Disorders","volume":" ","pages":""},"PeriodicalIF":0.8,"publicationDate":"2022-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"44508416","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-11-24DOI: 10.14785/lymphosign-2022-0008
A. Adedeji, I. Suleiman, O. G. Ayelagbe
ABSTRACT Background:Polyclonal hypergammaglobulinemia (PHGG) is commonly associated with liver disorders, andit could signify enhanced or defective immune system. This study was to determine the distribution and significance of PHGG in phases of chronic hepatitis B infection (CHB). Methods:Serum protein electrophoresis and colorimetric protein were assayed in 80 inactive (IA), 45 immune clearance (IC) and 17 immune escape (IE) CHB participants. ANOVA and Student’s t-test were used for the comparisons of data, while area under curve (AUC) was used to assess the performance. Results:A significant elevation was observed in gamma globulin in the three phases studied in relation to non-HBV infected control. The incidence of PHGG in different phases of CHB are; IA (61.3%), IC (33.3%) and IE (29.4%).IA phase; the least severe phase has the highest incidence of PHGG. Conclusion:Occurrence PHGG seems to signify enhances immune responses. Also, it could be used to some extent to predict IA phase. Keywords: Polyclonal hypergammaglobulinemia, Hepatitis B virus (HBV), Electrophoresis, CHB Statement of novelty: This study utilized both qualitative and quantitative methods of protein assay to evaluate the patterns of PHGG in untreated and categorized CHB infections.
{"title":"Distribution of Polyclonal Hypergammaglobulinemia in Different Stages of Chronic Hepatitis B Infection","authors":"A. Adedeji, I. Suleiman, O. G. Ayelagbe","doi":"10.14785/lymphosign-2022-0008","DOIUrl":"https://doi.org/10.14785/lymphosign-2022-0008","url":null,"abstract":"ABSTRACT Background:Polyclonal hypergammaglobulinemia (PHGG) is commonly associated with liver disorders, andit could signify enhanced or defective immune system. This study was to determine the distribution and significance of PHGG in phases of chronic hepatitis B infection (CHB). Methods:Serum protein electrophoresis and colorimetric protein were assayed in 80 inactive (IA), 45 immune clearance (IC) and 17 immune escape (IE) CHB participants. ANOVA and Student’s t-test were used for the comparisons of data, while area under curve (AUC) was used to assess the performance. Results:A significant elevation was observed in gamma globulin in the three phases studied in relation to non-HBV infected control. The incidence of PHGG in different phases of CHB are; IA (61.3%), IC (33.3%) and IE (29.4%).IA phase; the least severe phase has the highest incidence of PHGG. Conclusion:Occurrence PHGG seems to signify enhances immune responses. Also, it could be used to some extent to predict IA phase. Keywords: Polyclonal hypergammaglobulinemia, Hepatitis B virus (HBV), Electrophoresis, CHB Statement of novelty: This study utilized both qualitative and quantitative methods of protein assay to evaluate the patterns of PHGG in untreated and categorized CHB infections.","PeriodicalId":53881,"journal":{"name":"LymphoSign Journal-The Journal of Inherited Immune Disorders","volume":" ","pages":""},"PeriodicalIF":0.8,"publicationDate":"2022-11-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41395136","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-08-31DOI: 10.14785/lymphosign-2022-0009
Jenny Garkaby, O. Scott, Laura Abrego Fuentes, L. Vong, Jessica Willett-Pachul, Myra Pereira, V. Kim, C. Roifman
Background: Since the onset of the COVID-19 pandemic, a main challenge for clinicians and public health decision-makers has revolved around risk stratification in vulnerable populations, in particular individuals with inborn errors of immunity (IEI). However, available reports of the clinical course of COVID-19 in patients with IEI show wide variability, from a complete lack of symptoms to severe and complicated disease. Objective: To present the clinical features and outcomes of SARS-CoV-2 infection in adult patients with IEI. Methods: A retrospective chart review involving patient characteristics and clinical course of SARS-CoV-2 infection between December 2021-July 2022. Results: Ten adult patients with IEI followed in our center were diagnosed with COVID-19, as determined by RT-PCR or rapid antigen test. IEI in this cohort included both humoral, combined immunodeficiencies and phagocytic defects, with an underlying lung comorbidity identified in 3 patients. Symptoms were mostly mild and self-limiting. No severe outcomes, complications or mortality were noted in this study. Conclusions: We suggest that patients affected by a wide range of both humoral and combined IEI may demonstrate resilience, while highlighting the possible protective effects of vaccination and immunoglobulin replacement in this population.
{"title":"Case series of COVID-19 outcomes in adult patients with inborn errors of immunity","authors":"Jenny Garkaby, O. Scott, Laura Abrego Fuentes, L. Vong, Jessica Willett-Pachul, Myra Pereira, V. Kim, C. Roifman","doi":"10.14785/lymphosign-2022-0009","DOIUrl":"https://doi.org/10.14785/lymphosign-2022-0009","url":null,"abstract":"Background: Since the onset of the COVID-19 pandemic, a main challenge for clinicians and public health decision-makers has revolved around risk stratification in vulnerable populations, in particular individuals with inborn errors of immunity (IEI). However, available reports of the clinical course of COVID-19 in patients with IEI show wide variability, from a complete lack of symptoms to severe and complicated disease. Objective: To present the clinical features and outcomes of SARS-CoV-2 infection in adult patients with IEI. Methods: A retrospective chart review involving patient characteristics and clinical course of SARS-CoV-2 infection between December 2021-July 2022. Results: Ten adult patients with IEI followed in our center were diagnosed with COVID-19, as determined by RT-PCR or rapid antigen test. IEI in this cohort included both humoral, combined immunodeficiencies and phagocytic defects, with an underlying lung comorbidity identified in 3 patients. Symptoms were mostly mild and self-limiting. No severe outcomes, complications or mortality were noted in this study. Conclusions: We suggest that patients affected by a wide range of both humoral and combined IEI may demonstrate resilience, while highlighting the possible protective effects of vaccination and immunoglobulin replacement in this population.","PeriodicalId":53881,"journal":{"name":"LymphoSign Journal-The Journal of Inherited Immune Disorders","volume":" ","pages":""},"PeriodicalIF":0.8,"publicationDate":"2022-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"48568634","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-08-31DOI: 10.14785/lymphosign-2022-0012
Vong Linda, C. Roifman
The race to protect against severe outcomes of coronavirus disease 2019 (COVID-19), caused by SARS-CoV-2, has spurred the rapid development and authorization of novel vaccines and treatments worldwide. Individuals infected with SARS-COV-2 may experience a wide spectrum of symptoms, from nil (asymptomatic), mild (fever, cough, and dyspnea), to more severe clinical course (including acute respiratory distress, pneumonia, renal failure, and death). While uptake of the recommended vaccines exceed 83% (fully vaccinated) within the Canadian population, levels of protection vary, especially in patients with PID who have abnormal humoral and cellular immune responses. At present, there are 6 COVID-19 treatments authorized for use in Canada. These include (i) neutralizing antibodies targeting the spike protein of SARS-COV-2 to prevent virus entry into healthy cells, and (ii) antivirals that inhibit the ability of the SARS-CoV-2 virus to replicate. We provide here a brief overview of the indications and dose of the currently available treatments.
{"title":"COVID-19 treatments","authors":"Vong Linda, C. Roifman","doi":"10.14785/lymphosign-2022-0012","DOIUrl":"https://doi.org/10.14785/lymphosign-2022-0012","url":null,"abstract":"The race to protect against severe outcomes of coronavirus disease 2019 (COVID-19), caused by SARS-CoV-2, has spurred the rapid development and authorization of novel vaccines and treatments worldwide. Individuals infected with SARS-COV-2 may experience a wide spectrum of symptoms, from nil (asymptomatic), mild (fever, cough, and dyspnea), to more severe clinical course (including acute respiratory distress, pneumonia, renal failure, and death). While uptake of the recommended vaccines exceed 83% (fully vaccinated) within the Canadian population, levels of protection vary, especially in patients with PID who have abnormal humoral and cellular immune responses. At present, there are 6 COVID-19 treatments authorized for use in Canada. These include (i) neutralizing antibodies targeting the spike protein of SARS-COV-2 to prevent virus entry into healthy cells, and (ii) antivirals that inhibit the ability of the SARS-CoV-2 virus to replicate. We provide here a brief overview of the indications and dose of the currently available treatments.","PeriodicalId":53881,"journal":{"name":"LymphoSign Journal-The Journal of Inherited Immune Disorders","volume":" ","pages":""},"PeriodicalIF":0.8,"publicationDate":"2022-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"47762309","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-08-30DOI: 10.14785/lymphosign-2022-0010
O. Scott, Jenny Garkaby, Laura Abrego Fuentes, Jessica Willett-Pachul, C. Roifman
Background: Eosinophilic gastrointestinal disease (EGID) is an umbrella term for a heterogeneous group of disorders affecting the GI tract. In contrast to the relatively common eosinophilic esophagitis (EoE), eosinophilic gastroenteritis (EGE) remains poorly understood in terms of both its pathophysiology and genetic etiology, while treatment options remain limited. Aim: To expand the genotypic spectrum of EGE and describe our long-term experience of treatment with ketotifen. Methods: Case report of a patient with EGE followed by our team for over 27 years. Results: Our patient was diagnosed with EGE at the age of 4 years, accompanied by multiple other atopic manifestations and serum eosinophilia. He was later diagnosed with a heterozygous variant in RUNX1, a gene implicated in multi-lineage hematopoiesis, inhibition of Th2 polarization and T-regulatory cell function. The patient has experienced long-term symptom improvement while treated with the mast-cell stabilizing H1 anti-histamine, ketotifen, with substantial symptomatic worsening after this agent was briefly stopped. Conclusion: we expand the genotypic spectrum of EGID etiology to include mutations in RUNX1, and suggest ketotifen as a viable option for patients with treatment-refractory EGE.
{"title":"A Novel Variant in RUNX1 in A Patient with Refractory Eosinophilic Gastrointestinal Disease and Long-Term Clinical Response to Ketotifen","authors":"O. Scott, Jenny Garkaby, Laura Abrego Fuentes, Jessica Willett-Pachul, C. Roifman","doi":"10.14785/lymphosign-2022-0010","DOIUrl":"https://doi.org/10.14785/lymphosign-2022-0010","url":null,"abstract":"Background: Eosinophilic gastrointestinal disease (EGID) is an umbrella term for a heterogeneous group of disorders affecting the GI tract. In contrast to the relatively common eosinophilic esophagitis (EoE), eosinophilic gastroenteritis (EGE) remains poorly understood in terms of both its pathophysiology and genetic etiology, while treatment options remain limited. Aim: To expand the genotypic spectrum of EGE and describe our long-term experience of treatment with ketotifen. Methods: Case report of a patient with EGE followed by our team for over 27 years. Results: Our patient was diagnosed with EGE at the age of 4 years, accompanied by multiple other atopic manifestations and serum eosinophilia. He was later diagnosed with a heterozygous variant in RUNX1, a gene implicated in multi-lineage hematopoiesis, inhibition of Th2 polarization and T-regulatory cell function. The patient has experienced long-term symptom improvement while treated with the mast-cell stabilizing H1 anti-histamine, ketotifen, with substantial symptomatic worsening after this agent was briefly stopped. Conclusion: we expand the genotypic spectrum of EGID etiology to include mutations in RUNX1, and suggest ketotifen as a viable option for patients with treatment-refractory EGE.","PeriodicalId":53881,"journal":{"name":"LymphoSign Journal-The Journal of Inherited Immune Disorders","volume":" ","pages":""},"PeriodicalIF":0.8,"publicationDate":"2022-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49088516","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-08-30DOI: 10.14785/lymphosign-2022-0011
Laura Abrego Fuentes, Mohammad Alsalamah
Background: Yellow Nail Syndrome is defined as a triad of lymphedema, respiratory symptoms, and nail discoloration. The precise etiology remains unknown, however it has been reported alongside a broad spectrum of conditions including malignancies, autoinflammatory diseases, and immunodeficiencies. Aim: To highlight the association between defects in the intracellular bacterial sensor NOD2 and Yellow Nail Syndrome. Methods: A retrospective review of the patient’s chart was performed, including family history, characteristics, immune laboratory evaluation, and genetics. Results: A 65-year-old female was referred to us for lymphedema and bronchiectasis. She had recurrent episodes of pneumonia, cellulitis, and oral ulcers. Bilateral lymphedema on her lower limbs up to the hip and discoloured yellow nails were reported. Given her clinical picture, she was diagnosed with Yellow Nail Syndrome. The immunological evaluation was unremarkable overall, with normal T cell subsets and function and adequate antibody titres. The genetic testing identified a heterozygous mutation in the NOD2 gene, c.2107C>T (p.Arg703Cys), considered a variant of uncertain significance. Conclusion: Heterozygous variants in NOD2 can result in a spectrum of autoimmune and autoinflammatory disorders, including Yellow Nail Syndrome Statement of Novelty: We describe a patient with Yellow Nail Syndrome, presenting with the classic triad of clinical features. Genetic evaluation identified a heterozygous variant in the NOD2 gene, which has been extensively associated with several autoinflammatory diseases, but not Yellow Nail Syndrome.
{"title":"Association between NOD2 and autoinflammation presenting as Yellow Nail Syndrome","authors":"Laura Abrego Fuentes, Mohammad Alsalamah","doi":"10.14785/lymphosign-2022-0011","DOIUrl":"https://doi.org/10.14785/lymphosign-2022-0011","url":null,"abstract":"Background: Yellow Nail Syndrome is defined as a triad of lymphedema, respiratory symptoms, and nail discoloration. The precise etiology remains unknown, however it has been reported alongside a broad spectrum of conditions including malignancies, autoinflammatory diseases, and immunodeficiencies. Aim: To highlight the association between defects in the intracellular bacterial sensor NOD2 and Yellow Nail Syndrome. Methods: A retrospective review of the patient’s chart was performed, including family history, characteristics, immune laboratory evaluation, and genetics. Results: A 65-year-old female was referred to us for lymphedema and bronchiectasis. She had recurrent episodes of pneumonia, cellulitis, and oral ulcers. Bilateral lymphedema on her lower limbs up to the hip and discoloured yellow nails were reported. Given her clinical picture, she was diagnosed with Yellow Nail Syndrome. The immunological evaluation was unremarkable overall, with normal T cell subsets and function and adequate antibody titres. The genetic testing identified a heterozygous mutation in the NOD2 gene, c.2107C>T (p.Arg703Cys), considered a variant of uncertain significance. Conclusion: Heterozygous variants in NOD2 can result in a spectrum of autoimmune and autoinflammatory disorders, including Yellow Nail Syndrome Statement of Novelty: We describe a patient with Yellow Nail Syndrome, presenting with the classic triad of clinical features. Genetic evaluation identified a heterozygous variant in the NOD2 gene, which has been extensively associated with several autoinflammatory diseases, but not Yellow Nail Syndrome.","PeriodicalId":53881,"journal":{"name":"LymphoSign Journal-The Journal of Inherited Immune Disorders","volume":" ","pages":""},"PeriodicalIF":0.8,"publicationDate":"2022-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45043484","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-05-30DOI: 10.14785/lymphosign-2022-0007
Laura Abrego Fuentes, Jenny Garkaby, Jessica Willett-Pachul, Abby Watts-Dickens, Meghan Fraser, V. Kim, C. Roifman
ABSTRACT Background: Forkhead-box protein N1 (FOXN1) plays a critical role in the proper development and function of thymic epithelial cells, required for T cell ontogeny. Homozygous variants in FOXN1 cause severe combined immunodeficiency (SCID), whereas heterozygous mutations are associated with variable presentations and over time, improving T cell function. Aim: To highlight the importance of broader genetic investigations to attain a definitive molecular diagnosis following abnormal newborn screening for SCID. Methods: Case report of a patient with immunodeficiency due to a novel de novo FOXN1 mutation. Results: The patient was identified following abnormal newborn screening for SCID in which T cell receptor excision circles were absent/very low. Initial immune investigations revealed severe T cell lymphopenia and poor lymphocyte function and she was diagnosed with T-B+NK+SCID. During work-up for hematopoietic stem cell transplantation, extensive genetic investigations identified a novel heterozygous mutation in FOXN1. A more conservative management approach was taken, and over the following months, the patient’s immune parameters improved. Conclusion: Newborn screening for SCID has facilitated the detection of SCID, as well as other T cell immunodeficiencies, before infectious complications and organ damage occur. Heterozygous mutations in FOXN1 are associated with more variable presentations including improving immune indices with age. Here, results of genetic investigations were essential for informing the management of this case. Statement of Novelty We report a novel heterozygous mutation in FOXN1, presenting initially as T-B+NK+ SCID with gradual improvement of immune parameters over time.
{"title":"Novel heterozygous FOXN1 mutation identified during newborn screening for severe combined immunodeficiency is associated with improving immune parameters","authors":"Laura Abrego Fuentes, Jenny Garkaby, Jessica Willett-Pachul, Abby Watts-Dickens, Meghan Fraser, V. Kim, C. Roifman","doi":"10.14785/lymphosign-2022-0007","DOIUrl":"https://doi.org/10.14785/lymphosign-2022-0007","url":null,"abstract":"ABSTRACT Background: Forkhead-box protein N1 (FOXN1) plays a critical role in the proper development and function of thymic epithelial cells, required for T cell ontogeny. Homozygous variants in FOXN1 cause severe combined immunodeficiency (SCID), whereas heterozygous mutations are associated with variable presentations and over time, improving T cell function. Aim: To highlight the importance of broader genetic investigations to attain a definitive molecular diagnosis following abnormal newborn screening for SCID. Methods: Case report of a patient with immunodeficiency due to a novel de novo FOXN1 mutation. Results: The patient was identified following abnormal newborn screening for SCID in which T cell receptor excision circles were absent/very low. Initial immune investigations revealed severe T cell lymphopenia and poor lymphocyte function and she was diagnosed with T-B+NK+SCID. During work-up for hematopoietic stem cell transplantation, extensive genetic investigations identified a novel heterozygous mutation in FOXN1. A more conservative management approach was taken, and over the following months, the patient’s immune parameters improved. Conclusion: Newborn screening for SCID has facilitated the detection of SCID, as well as other T cell immunodeficiencies, before infectious complications and organ damage occur. Heterozygous mutations in FOXN1 are associated with more variable presentations including improving immune indices with age. Here, results of genetic investigations were essential for informing the management of this case. Statement of Novelty We report a novel heterozygous mutation in FOXN1, presenting initially as T-B+NK+ SCID with gradual improvement of immune parameters over time.","PeriodicalId":53881,"journal":{"name":"LymphoSign Journal-The Journal of Inherited Immune Disorders","volume":" ","pages":""},"PeriodicalIF":0.8,"publicationDate":"2022-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"44207516","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Introduction: DiGeorge syndrome is a heterogenous disorder with various clinical presentations. Common features of 22q11.2 deletion syndrome include thymic hypoplasia T-cell lymphopenia, conotruncal heart defects, facial dysmorphism, cleft palate, developmental delay and hypoparathyroidism. The severity of the condition varies, however typical presentation includes congenital heart defects and characteristic facial features. Isolated hypocalcemia in DiGeorge syndrome is rarely seen in as the sole manifestation in older teenagers of adults Aim: To report a case of an atypical presentation of DiGeorge syndrome Results: We report here a case of an infant who was diagnosed with DiGeorge syndrome with seizures being the only clinical manifestation displayed by the patient. He was found to have low TRECs on a newborn screen for severe combined immunodeficiency. He did not have facial dysmorphism nor cardiac defect. Conclusion: Our case showed that severe hypocalcemia can be the only presenting symptom in DiGeorge syndrome, based on this case we recommend physicians to test for calcium levels and PTH at the first encounter with a positive NBS for SCID.
{"title":"An Unusual Presentation of DiGeorge Syndrome","authors":"Jenny Garkaby, Laura Abrego Fuentes, Jessica Willett-Pachul, Abby Watts-Dickens, Meghan Fraser","doi":"10.14785/lymphosign-2022-0005","DOIUrl":"https://doi.org/10.14785/lymphosign-2022-0005","url":null,"abstract":"Introduction: DiGeorge syndrome is a heterogenous disorder with various clinical presentations. Common features of 22q11.2 deletion syndrome include thymic hypoplasia T-cell lymphopenia, conotruncal heart defects, facial dysmorphism, cleft palate, developmental delay and hypoparathyroidism. The severity of the condition varies, however typical presentation includes congenital heart defects and characteristic facial features. Isolated hypocalcemia in DiGeorge syndrome is rarely seen in as the sole manifestation in older teenagers of adults Aim: To report a case of an atypical presentation of DiGeorge syndrome Results: We report here a case of an infant who was diagnosed with DiGeorge syndrome with seizures being the only clinical manifestation displayed by the patient. He was found to have low TRECs on a newborn screen for severe combined immunodeficiency. He did not have facial dysmorphism nor cardiac defect. Conclusion: Our case showed that severe hypocalcemia can be the only presenting symptom in DiGeorge syndrome, based on this case we recommend physicians to test for calcium levels and PTH at the first encounter with a positive NBS for SCID.","PeriodicalId":53881,"journal":{"name":"LymphoSign Journal-The Journal of Inherited Immune Disorders","volume":" ","pages":""},"PeriodicalIF":0.8,"publicationDate":"2022-05-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"48701088","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-05-23DOI: 10.14785/lymphosign-2022-0006
Vong Linda, C. Roifman
Over the past 2 years since the pandemic took hold, those with primary immunodeficiency (PID) have been advised to practice rigorous social distancing, hand hygiene, and if appropriate – COVID-19 vaccination, given the assumption of more severe outcomes. During this period, studies examining the effectiveness of the COVID-19 vaccine and longevity of antibody titers have been instrumental in guiding the need for additional ‘boosters’, allowing for additional protection due to insufficient seroconversion – the development of specific antibodies following vaccination (or exposure to an infectious agent), or waning immunity. Here, we review current data on humoral and cellular responses to the COVID-19 vaccine in individuals with PID, as well as disease course and outcomes of individuals in this cohort who were infected with the SARS-CoV-2 virus.
{"title":"COVID-19 outcomes in immunocompromised individuals: seroconversion and vaccine effectiveness","authors":"Vong Linda, C. Roifman","doi":"10.14785/lymphosign-2022-0006","DOIUrl":"https://doi.org/10.14785/lymphosign-2022-0006","url":null,"abstract":"Over the past 2 years since the pandemic took hold, those with primary immunodeficiency (PID) have been advised to practice rigorous social distancing, hand hygiene, and if appropriate – COVID-19 vaccination, given the assumption of more severe outcomes. During this period, studies examining the effectiveness of the COVID-19 vaccine and longevity of antibody titers have been instrumental in guiding the need for additional ‘boosters’, allowing for additional protection due to insufficient seroconversion – the development of specific antibodies following vaccination (or exposure to an infectious agent), or waning immunity. Here, we review current data on humoral and cellular responses to the COVID-19 vaccine in individuals with PID, as well as disease course and outcomes of individuals in this cohort who were infected with the SARS-CoV-2 virus.","PeriodicalId":53881,"journal":{"name":"LymphoSign Journal-The Journal of Inherited Immune Disorders","volume":"1 1","pages":""},"PeriodicalIF":0.8,"publicationDate":"2022-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41377266","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-05-19DOI: 10.14785/lymphosign-2022-0004
Jenny Garkaby, Laura Abrego Fuentes, Jessica Willett-Pachul, L. Vong
Background: Cytotoxic T lymphocyte-associated antigen-4 (CTLA4) haploinsufficiency is characterized by a variety of phenotypes, ranging from autoimmune disorders, enteropathy, fatal combined immunodeficiency, as well as lymphoproliferation and malignancy. Aim: To broaden the genotypic spectrum and clinical presentations of patients with CTLA4 variants. Methods: We evaluated a female patient with autoimmunity and lymphopenia. Immune workup and whole exome sequencing (WES) were performed. Results: The proband presented at 11 years of age with hypothyroidism, and later developed Evans syndrome, alopecia, eczema, and lymphocytic interstitial pneumonia. Immune evaluation revealed T, B, and NK lymphopenia with normal humoral immunity. Following a negative genetic panel for autoimmune lymphoproliferative syndrome (ALPS), WES analysis showed a novel heterozygous intronic variant predicted in-silico to causing skipping of exon 2 of the CTLA4 gene. Conclusion: A novel heterozygous mutation in CTLA4 caused variable presentations of immune dysregulation, one of the hallmarks of CTLA4 haploinsufficiency. Statement of Novelty: We herein report a novel mutation in CTLA4 resulting in various features of autoimmunity.
{"title":"CTLA4 haploinsufficiency caused by a novel heterozygous splice site mutation","authors":"Jenny Garkaby, Laura Abrego Fuentes, Jessica Willett-Pachul, L. Vong","doi":"10.14785/lymphosign-2022-0004","DOIUrl":"https://doi.org/10.14785/lymphosign-2022-0004","url":null,"abstract":"Background: Cytotoxic T lymphocyte-associated antigen-4 (CTLA4) haploinsufficiency is characterized by a variety of phenotypes, ranging from autoimmune disorders, enteropathy, fatal combined immunodeficiency, as well as lymphoproliferation and malignancy. Aim: To broaden the genotypic spectrum and clinical presentations of patients with CTLA4 variants. Methods: We evaluated a female patient with autoimmunity and lymphopenia. Immune workup and whole exome sequencing (WES) were performed. Results: The proband presented at 11 years of age with hypothyroidism, and later developed Evans syndrome, alopecia, eczema, and lymphocytic interstitial pneumonia. Immune evaluation revealed T, B, and NK lymphopenia with normal humoral immunity. Following a negative genetic panel for autoimmune lymphoproliferative syndrome (ALPS), WES analysis showed a novel heterozygous intronic variant predicted in-silico to causing skipping of exon 2 of the CTLA4 gene. Conclusion: A novel heterozygous mutation in CTLA4 caused variable presentations of immune dysregulation, one of the hallmarks of CTLA4 haploinsufficiency. Statement of Novelty: We herein report a novel mutation in CTLA4 resulting in various features of autoimmunity.","PeriodicalId":53881,"journal":{"name":"LymphoSign Journal-The Journal of Inherited Immune Disorders","volume":" ","pages":""},"PeriodicalIF":0.8,"publicationDate":"2022-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"47483491","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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