Mendelian Susceptibility to Mycobacterial Disease with Signal Peptide Peptidase-like 2A (SPPL2A) Deficiency: A Case Report
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Abstract
Mendelian susceptibility to mycobacterial disease (MSMD) is a rare genetic disorder characterized by immunodeficiency, leading to increased susceptibility to mycobacterial infections. Studies have identified several genes that are associated with MSMD in the interferon-gamma/interleukin (IL)-12/IL-23 signaling pathway.
One of these genes is signal peptide peptidase-like 2A (SPPL2A), which is very rare, and defects in this gene have been reported only in 3 patients with MSMD. This case report presents the rare SPPL2A deficiency with an abnormal presentation, which adds to the limited number of these genetic defects.
This report presents the case of a 1-year-old boy who developed Bacillus Calmette-Guerin infection (BCGitis), lymphadenopathy, and an arm abscess that required surgical drainage following BCG vaccination. The patient had hypogammaglobulinemia, normal B-cell counts, normal CD4 counts, low CD8 counts, and SPPL2A deficiency, which is related to MSMD. The patient received a second line of anti-tuberculosis agents.
SPPL2A deficiency is associated with MSMD and can cause severe BCGitis and disruption of immunoglobulin production.
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3. Fallah F, Nasiri MJ, Pormohammad A. Bacillus Calmette-Guerin (BCG) vaccine in Iran. J Clin Tuberc Other Mycobact Dis. 2018;11:22.
4. Ying W, Sun J, Liu D, Hui X, Yu Y, Wang J, et al. Clinical characteristics and immunogenetics of BCGosis/BCGitis in Chinese children: a 6 year follow-up study. PLoS One. 2014;9(4):e94485.
5. Shrot S, Barkai G, Ben-Shlush A, Soudack M. BCGitis and BCGosis in children with primary immunodeficiency - imaging characteristics. Pediatr Radiol. 2016;46(2):237-45.
6. Movahedi M, Jamee M, Ghaffaripour H, Noori F, Ghaini M, Eskandarzadeh S, et al. Pulmonary manifestations in a cohort of patients with inborn errors of immunity: an 8-year follow-up study. Allergol Immunopathol (Madr). 2022;50(1):80-4.
7. Khalili N, Mohammadzadeh I, Khalili N, Heredia RJ, Zoghi S, Boztug K, et al. BCGitis as the primary manifestation of chronic granulomatous disease. ID Cases. 2021;23:e01038.
8. Bernatowska E, Pac M, Heropolitańska-Pliszka E, Pietrucha B, Dąbrowska-Leonik N, Skomska-Pawliszak M, et al. BCG Moreau Polish Substrain Infections in Patients With Inborn Errors of Immunity: 40 Years of Experience in the Department of Immunology, Children's Memorial Health Institute, Warsaw. Front Pediatr. 2022;10:839111.
9. Xia L, Liu XH, Yuan Y, Lowrie DB, Fan XY, Li T, et al. An Updated Review on MSMD Research Globally and A Literature Review on the Molecular Findings, Clinical Manifestations, and Treatment Approaches in China. Front Immunol. 2022;13:926781.
10. Bustamante J. Mendelian susceptibility to mycobacterial disease: recent discoveries. Hum Genet. 2020;139(6-7):993-1000.
11. Norouzi S, Aghamohammadi A, Mamishi S, Rosenzweig SD, Rezaei N. Bacillus Calmette-Guérin (BCG) complications associated with primary immunodeficiency diseases. J Infect. 2012;64(6):543-54.
12. Kong XF, Martinez-Barricarte R, Kennedy J, Mele F, Lazarov T, Deenick EK, et al. Disruption of an anti-mycobacterial circuit between dendritic and helper T cells in human SPPL2a deficiency. Nat Immunol. 2018;19(9):973-85.
13. Justiz-Vaillant AA, Hoyte T, Davis N, Deonarinesingh C, De Silva A, Dhanpaul D, et al. A Systematic Review of the Clinical Diagnosis of Transient Hypogammaglobulinemia of Infancy. Children (Basel). 2023;10(8).
14. Gradtke AC, Mentrup T, Lehmann CHK, Cabrera-Cabrera F, Desel C, Okakpu D, et al. Deficiency of the Intramembrane Protease SPPL2a Alters Anti-mycobacterial Cytokine Responses of Dendritic Cells. J Immunol. 2021;206(1):164-80.
15. Bustamante J. Mendelian susceptibility to mycobacterial disease: recent discoveries. Hum Gen. 2020;139(6):993-1000.
16. Mahdaviani SA, Mansouri D, Jamee M, Zaki-Dizaji M, Aghdam KR, Mortaz E, et al. Mendelian Susceptibility to Mycobacterial Disease (MSMD): Clinical and Genetic Features of 32 Iranian Patients. J Clin Immunol. 2020;40(6):872-82.
17. Gebeyehu NA, Deribessa SJ, Alexandra F, Demissie MT, Mihretu Gebre W, Gebremariam AM, et al. Mendelian Susceptibility to Mycobacterial Diseases (MSMD) in a 13-Year-Old Ethiopian Girl with Autosomal Dominant Interferon Gamma Receptor 1(IFN-γ R1) Defect: A Clinical Diagnostic and Treatment Challenge. Case Rep Infect Dis. 2022;2022:6534009.
18. Mahdaviani SA, Fallahi M, Jamee M, Marjani M, Tabarsi P, Moniri A, et al. Effective anti-mycobacterial treatment for BCG disease in patients with Mendelian Susceptibility to Mycobacterial Disease (MSMD): a case series. Ann Clin Microbiol Antimicrobials. 2022;21(1):8.
19. Olbrich P, Martínez-Saavedra MT, Perez-Hurtado JM, Sanchez C, Sanchez B, Deswarte C, et al. Diagnostic and therapeutic challenges in a child with complete interferon-γ receptor 1 deficiency. Ped Blood Cancer. 2015;62(11):2036-9.
20. Noma K, Mizoguchi Y, Tsumura M, Okada S. Mendelian susceptibility to mycobacterial diseases: state of the art. Clin Microbiol Infec. 2022;28(11):1429-34.
2. Rosain J, Kong XF, Martinez-Barricarte R, Oleaga-Quintas C, Ramirez-Alejo N, Markle J, et al. Mendelian susceptibility to mycobacterial disease: 2014-2018 update. Immunol Cell Biol. 2019;97(4):360-7.
3. Fallah F, Nasiri MJ, Pormohammad A. Bacillus Calmette-Guerin (BCG) vaccine in Iran. J Clin Tuberc Other Mycobact Dis. 2018;11:22.
4. Ying W, Sun J, Liu D, Hui X, Yu Y, Wang J, et al. Clinical characteristics and immunogenetics of BCGosis/BCGitis in Chinese children: a 6 year follow-up study. PLoS One. 2014;9(4):e94485.
5. Shrot S, Barkai G, Ben-Shlush A, Soudack M. BCGitis and BCGosis in children with primary immunodeficiency - imaging characteristics. Pediatr Radiol. 2016;46(2):237-45.
6. Movahedi M, Jamee M, Ghaffaripour H, Noori F, Ghaini M, Eskandarzadeh S, et al. Pulmonary manifestations in a cohort of patients with inborn errors of immunity: an 8-year follow-up study. Allergol Immunopathol (Madr). 2022;50(1):80-4.
7. Khalili N, Mohammadzadeh I, Khalili N, Heredia RJ, Zoghi S, Boztug K, et al. BCGitis as the primary manifestation of chronic granulomatous disease. ID Cases. 2021;23:e01038.
8. Bernatowska E, Pac M, Heropolitańska-Pliszka E, Pietrucha B, Dąbrowska-Leonik N, Skomska-Pawliszak M, et al. BCG Moreau Polish Substrain Infections in Patients With Inborn Errors of Immunity: 40 Years of Experience in the Department of Immunology, Children's Memorial Health Institute, Warsaw. Front Pediatr. 2022;10:839111.
9. Xia L, Liu XH, Yuan Y, Lowrie DB, Fan XY, Li T, et al. An Updated Review on MSMD Research Globally and A Literature Review on the Molecular Findings, Clinical Manifestations, and Treatment Approaches in China. Front Immunol. 2022;13:926781.
10. Bustamante J. Mendelian susceptibility to mycobacterial disease: recent discoveries. Hum Genet. 2020;139(6-7):993-1000.
11. Norouzi S, Aghamohammadi A, Mamishi S, Rosenzweig SD, Rezaei N. Bacillus Calmette-Guérin (BCG) complications associated with primary immunodeficiency diseases. J Infect. 2012;64(6):543-54.
12. Kong XF, Martinez-Barricarte R, Kennedy J, Mele F, Lazarov T, Deenick EK, et al. Disruption of an anti-mycobacterial circuit between dendritic and helper T cells in human SPPL2a deficiency. Nat Immunol. 2018;19(9):973-85.
13. Justiz-Vaillant AA, Hoyte T, Davis N, Deonarinesingh C, De Silva A, Dhanpaul D, et al. A Systematic Review of the Clinical Diagnosis of Transient Hypogammaglobulinemia of Infancy. Children (Basel). 2023;10(8).
14. Gradtke AC, Mentrup T, Lehmann CHK, Cabrera-Cabrera F, Desel C, Okakpu D, et al. Deficiency of the Intramembrane Protease SPPL2a Alters Anti-mycobacterial Cytokine Responses of Dendritic Cells. J Immunol. 2021;206(1):164-80.
15. Bustamante J. Mendelian susceptibility to mycobacterial disease: recent discoveries. Hum Gen. 2020;139(6):993-1000.
16. Mahdaviani SA, Mansouri D, Jamee M, Zaki-Dizaji M, Aghdam KR, Mortaz E, et al. Mendelian Susceptibility to Mycobacterial Disease (MSMD): Clinical and Genetic Features of 32 Iranian Patients. J Clin Immunol. 2020;40(6):872-82.
17. Gebeyehu NA, Deribessa SJ, Alexandra F, Demissie MT, Mihretu Gebre W, Gebremariam AM, et al. Mendelian Susceptibility to Mycobacterial Diseases (MSMD) in a 13-Year-Old Ethiopian Girl with Autosomal Dominant Interferon Gamma Receptor 1(IFN-γ R1) Defect: A Clinical Diagnostic and Treatment Challenge. Case Rep Infect Dis. 2022;2022:6534009.
18. Mahdaviani SA, Fallahi M, Jamee M, Marjani M, Tabarsi P, Moniri A, et al. Effective anti-mycobacterial treatment for BCG disease in patients with Mendelian Susceptibility to Mycobacterial Disease (MSMD): a case series. Ann Clin Microbiol Antimicrobials. 2022;21(1):8.
19. Olbrich P, Martínez-Saavedra MT, Perez-Hurtado JM, Sanchez C, Sanchez B, Deswarte C, et al. Diagnostic and therapeutic challenges in a child with complete interferon-γ receptor 1 deficiency. Ped Blood Cancer. 2015;62(11):2036-9.
20. Noma K, Mizoguchi Y, Tsumura M, Okada S. Mendelian susceptibility to mycobacterial diseases: state of the art. Clin Microbiol Infec. 2022;28(11):1429-34.
| Files | ||
| Issue | Vol 23 No 5 (2024) | |
| Section | Case Report(s) | |
| DOI | https://doi.org/10.18502/ijaai.v23i5.16753 | |
| Keywords | ||
| Bacillus calmette-guerin infection Mendelian susceptibility to mycobacterial disease Signal peptide peptidase-like 2A deficiency Signal peptide peptidase | ||
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This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License. |
How to Cite
1.
Esmaeilzadeh H, Pouladfar G, Gholami MA, Mohtadi H. Mendelian Susceptibility to Mycobacterial Disease with Signal Peptide Peptidase-like 2A (SPPL2A) Deficiency: A Case Report. Iran J Allergy Asthma Immunol. 2024;23(5):588-593.
