Activated phosphoinositide 3-kinase delta syndrome 1 and 2 (APDS 1 and APDS 2): similarities and differences based on clinical presentation in two boys
Abstract Background Activated PI3K delta syndrome (APDS) belongs to the heterogeneous group of primary immunodeficiency disorders (PIDs). Progress in next-generation sequencing (NGS) enabled identification of gain-of-function mutations in phosphoinositide 3-kinase (PI3K) genes. Depending on the type...
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| Format: | Article |
| Language: | English |
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BMC
2020-04-01
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| Series: | Allergy, Asthma & Clinical Immunology |
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| Online Access: | http://link.springer.com/article/10.1186/s13223-020-00420-6 |
| _version_ | 1819160837715132416 |
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| author | Marlena Ewertowska Elżbieta Grześk Anna Urbańczyk Anna Dąbrowska Katarzyna Bąbol-Pokora Monika Łęcka Sylwia Kołtan |
| author_facet | Marlena Ewertowska Elżbieta Grześk Anna Urbańczyk Anna Dąbrowska Katarzyna Bąbol-Pokora Monika Łęcka Sylwia Kołtan |
| author_sort | Marlena Ewertowska |
| collection | DOAJ |
| description | Abstract Background Activated PI3K delta syndrome (APDS) belongs to the heterogeneous group of primary immunodeficiency disorders (PIDs). Progress in next-generation sequencing (NGS) enabled identification of gain-of-function mutations in phosphoinositide 3-kinase (PI3K) genes. Depending on the type of causative mutation, APDS is classified into two types: APDS 1 and APDS 2. To date, less than 100 cases of APDS have been reported. Clinical symptoms of APDS result from impaired immune regulation and are clinically manifested by recurrent infections, allergies, lymphoproliferation and autoimmunity. They show similarity to other PIDs. Therefore, many patients were diagnosed incorrectly. The availability of genetic testing has allowed establishing the correct diagnosis in increasing number of patients suffering from APDS. Case presentations The first male patient presented in infancy with recurrent infections. Subsequently he was found to suffer from hepatosplenomegaly, early portal hypertension, massive lymphoproliferation and hypogammaglobulinemia. The common E1021K mutation in the PI3KCD gene was identified. The patient underwent successful hematopoietic stem cell transplantation with resolution of most symptoms. The second patient suffered from persistent growth retardation since early life, facial dysmorphism and recurrent respiratory infections from early childhood. He was found to have systemic lympho-proliferation, panhypoglobulinemia and impaired antibody responses to vaccines. The introduction of NGS in Poland enabled rapid identification of a mutation in the PI3KR1 gene. Growth hormone administration seemed to have worsened the lymphoproliferation. Conclusions Patients with suspected common variable immunodeficiency (CVID) and additional symptoms, such as allergy, facial dysmorphia, short stature, enhanced lymphoproliferation and lack of adequate response to human immunoglobulin replacement therapy, should be considered for NGS-based genetic testing. It may substantially shorten the time needed to establish the correct diagnosis, direct appropriate treatment and avoid potentially harmful therapies. To date, few cases of APDS have been described. It is important to report each of them to establish clinical indices and laboratory biomarkers of APDS 1 and APDS 2, to develop the standards of care in these conditions. |
| first_indexed | 2024-12-22T17:02:48Z |
| format | Article |
| id | doaj.art-8e98c61eb52b445ab91a9fb440120c47 |
| institution | Directory Open Access Journal |
| issn | 1710-1492 |
| language | English |
| last_indexed | 2024-12-22T17:02:48Z |
| publishDate | 2020-04-01 |
| publisher | BMC |
| record_format | Article |
| series | Allergy, Asthma & Clinical Immunology |
| spelling | doaj.art-8e98c61eb52b445ab91a9fb440120c472022-12-21T18:19:17ZengBMCAllergy, Asthma & Clinical Immunology1710-14922020-04-011611710.1186/s13223-020-00420-6Activated phosphoinositide 3-kinase delta syndrome 1 and 2 (APDS 1 and APDS 2): similarities and differences based on clinical presentation in two boysMarlena Ewertowska0Elżbieta Grześk1Anna Urbańczyk2Anna Dąbrowska3Katarzyna Bąbol-Pokora4Monika Łęcka5Sylwia Kołtan6Faculty of Medicine, Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in ToruńDepartment of Paediatrics, Hematology and Oncology, Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in ToruńFaculty of Medicine, Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in ToruńDepartment of Paediatrics, Hematology and Oncology, Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in ToruńDepartment of Paediatrics, Oncology, Hematology and Diabetology, Medical University of ŁódźDepartment of Paediatrics, Hematology and Oncology, Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in ToruńDepartment of Paediatrics, Hematology and Oncology, Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in ToruńAbstract Background Activated PI3K delta syndrome (APDS) belongs to the heterogeneous group of primary immunodeficiency disorders (PIDs). Progress in next-generation sequencing (NGS) enabled identification of gain-of-function mutations in phosphoinositide 3-kinase (PI3K) genes. Depending on the type of causative mutation, APDS is classified into two types: APDS 1 and APDS 2. To date, less than 100 cases of APDS have been reported. Clinical symptoms of APDS result from impaired immune regulation and are clinically manifested by recurrent infections, allergies, lymphoproliferation and autoimmunity. They show similarity to other PIDs. Therefore, many patients were diagnosed incorrectly. The availability of genetic testing has allowed establishing the correct diagnosis in increasing number of patients suffering from APDS. Case presentations The first male patient presented in infancy with recurrent infections. Subsequently he was found to suffer from hepatosplenomegaly, early portal hypertension, massive lymphoproliferation and hypogammaglobulinemia. The common E1021K mutation in the PI3KCD gene was identified. The patient underwent successful hematopoietic stem cell transplantation with resolution of most symptoms. The second patient suffered from persistent growth retardation since early life, facial dysmorphism and recurrent respiratory infections from early childhood. He was found to have systemic lympho-proliferation, panhypoglobulinemia and impaired antibody responses to vaccines. The introduction of NGS in Poland enabled rapid identification of a mutation in the PI3KR1 gene. Growth hormone administration seemed to have worsened the lymphoproliferation. Conclusions Patients with suspected common variable immunodeficiency (CVID) and additional symptoms, such as allergy, facial dysmorphia, short stature, enhanced lymphoproliferation and lack of adequate response to human immunoglobulin replacement therapy, should be considered for NGS-based genetic testing. It may substantially shorten the time needed to establish the correct diagnosis, direct appropriate treatment and avoid potentially harmful therapies. To date, few cases of APDS have been described. It is important to report each of them to establish clinical indices and laboratory biomarkers of APDS 1 and APDS 2, to develop the standards of care in these conditions.http://link.springer.com/article/10.1186/s13223-020-00420-6PI3KδPrimary immunodeficiencyAPDSHyper IgMGrowth hormoneGenetic testing |
| spellingShingle | Marlena Ewertowska Elżbieta Grześk Anna Urbańczyk Anna Dąbrowska Katarzyna Bąbol-Pokora Monika Łęcka Sylwia Kołtan Activated phosphoinositide 3-kinase delta syndrome 1 and 2 (APDS 1 and APDS 2): similarities and differences based on clinical presentation in two boys Allergy, Asthma & Clinical Immunology PI3Kδ Primary immunodeficiency APDS Hyper IgM Growth hormone Genetic testing |
| title | Activated phosphoinositide 3-kinase delta syndrome 1 and 2 (APDS 1 and APDS 2): similarities and differences based on clinical presentation in two boys |
| title_full | Activated phosphoinositide 3-kinase delta syndrome 1 and 2 (APDS 1 and APDS 2): similarities and differences based on clinical presentation in two boys |
| title_fullStr | Activated phosphoinositide 3-kinase delta syndrome 1 and 2 (APDS 1 and APDS 2): similarities and differences based on clinical presentation in two boys |
| title_full_unstemmed | Activated phosphoinositide 3-kinase delta syndrome 1 and 2 (APDS 1 and APDS 2): similarities and differences based on clinical presentation in two boys |
| title_short | Activated phosphoinositide 3-kinase delta syndrome 1 and 2 (APDS 1 and APDS 2): similarities and differences based on clinical presentation in two boys |
| title_sort | activated phosphoinositide 3 kinase delta syndrome 1 and 2 apds 1 and apds 2 similarities and differences based on clinical presentation in two boys |
| topic | PI3Kδ Primary immunodeficiency APDS Hyper IgM Growth hormone Genetic testing |
| url | http://link.springer.com/article/10.1186/s13223-020-00420-6 |
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