Written and peer-reviewed by physicians—but use at your own risk. Read our disclaimer.

banner image

amboss

Trusted medical answers—in seconds.

Get access to 1,000+ medical articles with instant search
and clinical tools.

Try free for 5 days

Congenital immunodeficiency disorders

Last updated: November 25, 2020

Summary

Congenital immunodeficiency disorders are characterized by a deficiency, absence, or defect in one or more of the main components of the immune system. These disorders are genetically determined and typically manifest during infancy and childhood as frequent, chronic, or opportunistic infections. Classification is based on the component of the immune system that is deficient, absent, or defective. The diagnosis is confirmed with tests such as differential WBC count, absolute lymphocyte count, quantitative immunoglobulin (Ig) measurements, and antibody titers. Treatment usually consists of prophylactic antibiotics to manage and prevent infections. The prognosis in congenital immunodeficiency disorders is variable and depends on the specific disorder.

Overview

Congenital B-cell immunodeficiencies

Immunodeficiency Etiology Clinical features Diagnostic findings
Bruton agammaglobulinemia
  • Onset: > 4 months after birth
  • Recurrent, severe pyogenic infections, especially by encapsulated organisms
  • Hypoplasia of lymphoid tissue
Selective IgA deficiency
Common variable immunodeficiency
  • Onset later than other B-cell defects (usually 20–35 years of age)
  • Recurrent sinopulmonary infections
  • Increased risk of lymphoma, autoimmune disorders, and bronchiectasis

Congenital T-cell immunodeficiencies

Immunodeficiency Etiology Clinical features Diagnostic findings
DiGeorge syndrome
Autosomal dominant hyper-IgE syndrome (Job syndrome)
  • Remember the acronym FATED
IL-12 receptor deficiency
  • Onset varies but usually 1–3 years of age
  • Disseminated disease, especially tuberculosis
  • Fungal infections
Chronic mucocutaneous candidiasis
IPEX syndrome

Congenital combined immunodeficiencies

Immunodeficiency Etiology Clinical features Diagnostic findings
Severe combined immunodeficiency
Wiskott-Aldrich syndrome (WAS)
Hyper-IgM syndrome
Ataxia telangiectasia

Congenital neutrophil and phagocyte disorders

Immunodeficiency Etiology Clinical features Diagnostic findings
Chronic granulomatous disease (CGD)
Leukocyte adhesion deficiency type 1
Chédiak-Higashi syndrome
Myeloperoxidase deficiency
  • Often asymptomatic
  • Recurrent Candida infections
Severe congenital neutropenia

Complement disorders

Immunodeficiency Etiology Clinical features Diagnostic findings
C1 esterase inhibitor deficiency
  • Recurrent angioedemas provoked by triggers, e.g., trauma, surgery, infections, and drugs
  • Airway edemas can be life-threatening.
Terminal complement deficiency
C3 deficiency

Congenital B-cell immunodeficiencies

B-cell defects (humoral immunity deficiencies) account for 50–60% of all primary immunodeficiencies.

Bruton agammaglobulinemia (X-linked agammaglobulinemia)

Live vaccines (e.g., MMR) are contraindicated in patients with Bruton agammaglobulinemia.

Selective IgA deficiency (SIgAD)

To prevent transfusion reactions, IgA-deficient patients must be given washed blood products without IgA or obtain blood from an IgA-deficient donor.

Common variable immunodeficiency (CVID)

References:[1][2][3][4][5][6][7]

Congenital T-cell immunodeficiencies

T-cell defects (cellular immunity deficiencies) are responsible for 5–10% of congenital immunodeficiencies.

DiGeorge syndrome (22q11.2 deletion syndrome)

CATCH-22 is the acronym for typical features of DiGeorge syndrome: Cardiac anomalies; Anomalous face; Thymic aplasia/hypoplasia; Cleft palate; Hypocalcemia; Chromosome 22.

Autosomal dominant hyperimmunoglobulin E syndrome (Job syndrome)

FATED is the acronym for the typical features of Autosomal dominant hyper-IgE syndrome: Coarse Facies/Fractures; Abscesses; Retained primary Teeth; Hyper-IgE/Eosinophilia); Dermatologic (severe eczema).

IL-12 receptor deficiency

Chronic mucocutaneous candidiasis

IPEX syndrome (Immune dysregulation, Polyendocrinopathy, Enteropathy, X-linked)

References:[9][10][11][12][13][14][15][16][17]

Congenital mixed immunodeficiencies

Severe combined immunodeficiency (SCID, bubble boy disease, Glanzmann–Riniker syndrome, alymphocytosis)

Wiskott-Aldrich syndrome (WAS)

WIPE is the acronym for the classic triad seen in Wiskott-Aldrich syndrome: Wiskott-Aldrich, Infections, Purpura, Eczema.

Hyper-IgM syndrome

Ataxia telangiectasia

References:[18][20][21][22][23]

Congenital neutrophil and phagocyte disorders

Phagocytic defects are characterized by the impaired ability of phagocytic cells (e.g., monocytes, macrophages, granulocytes such as neutrophils and eosinophils) to kill pathogens. These types of defects account for 10–15% of primary immunodeficiencies.

Chronic granulomatous disease (CGD)

Leukocyte adhesion deficiency type 1 (LAD1)

Chédiak-Higashi syndrome

Myeloperoxidase deficiency

Severe congenital neutropenia

References:[13][20][24][25]

Congenital complement deficiencies

Complement deficiencies are rare (≤ 2%) deficiencies of complement components or inhibitors.

C1 esterase inhibitor deficiency (hereditary angioedema)

See bradykinin-mediated angioedema in angioedema.

Terminal complement deficiency (C5–C9 deficiency)

C3 deficiency

References:[20][22][26][27][28]

References

  1. Wissem Hafsi, Talel Badri. Job Syndrome (Hyperimmunoglobulin E). StatPearls Publishing. 2019 .
  2. Estupiñan BA. Chronic Mucocutaneous Candidiasis. In: Elston DM, Chronic Mucocutaneous Candidiasis. New York, NY: WebMD. https://emedicine.medscape.com/article/1091928. Updated: April 17, 2017. Accessed: May 14, 2018.
  3. Kasper DL, Fauci AS, Hauser SL, Longo DL, Lameson JL, Loscalzo J. Harrison's Principles of Internal Medicine. McGraw-Hill Education ; 2015
  4. Caragol I, Casanova JL. Inherited disorders of the Interleukin-12/ Interferon-gamma axis: Mendelian predisposition to mycobacterial disease in man. Inmunología. 2003; 22 (3): p.263-276.
  5. Palamaro L, Giardino G, Santamaria F et al . Interleukin 12 receptor deficiency in a child with recurrent bronchopneumonia and very high IgE levels. Ital J Pediatr. 2012; 38 (46). doi: 10.1186/1824-7288-38-46 . | Open in Read by QxMD
  6. Prando C, Samarina A, Bustamante J et al. . Inherited IL-12p40 deficiency. Medicine (Baltimore). 2013; 92 (2): p.109-122. doi: 10.1097/MD.0b013e31828a01f9 . | Open in Read by QxMD
  7. Edgar JDM. Immunology. Elsevier Health Sciences ; 2006
  8. Fomin AB, Pastorino AC, Kim CA, Pereira C, Carneiro-Sampaio M, Abe-Jacob CM. DiGeorge Syndrome: a not so rare disease. Clinics. 2010; 65 (9): p.865-869. doi: 10.1590/s1807-59322010000900009 . | Open in Read by QxMD
  9. Khan K, Wozniak SE, Giannone AL, Abdulmassih ME. A boy with relentless pruritus: Job’s Syndrome. Am J Case Rep. 2016; 17 : p.104-110. doi: 10.12659/ajcr.896798 . | Open in Read by QxMD
  10. Murphy KM. Janeway's Immunobiology. Garland Science ; 2011
  11. Puck JM, Stiehm ER, TePas E. UpToDate - Severe Combined Immunodeficiency (SCID): An Overview. In: Post TW, ed. UpToDate. Waltham, MA: UpToDate. https://www.uptodate.com/contents/severe-combined-immunodeficiency-scid-an-overview.Last updated: April 18, 2018. Accessed: July 19, 2018.
  12. Mary Dell Railey, M.D., Yuliya Lokhnygina, Ph.D., and Rebecca H. Buckley, M.D.. Long Term Clinical Outcome of Patients with Severe Combined Immunodeficiency who Received Related Donor Bone Marrow Transplants without Pre-transplant Chemotherapy or Post-transplant GVHD Prophylaxis. The Journal of Pediatrics. 2009 .
  13. Le T, Bhushan V, Chen V, King M. First Aid for the USMLE Step 2 CK. McGraw-Hill Education ; 2015
  14. X-Linked Hyper IgM Syndrome.
  15. Le T, Bhushan V,‎ Sochat M, Chavda Y, Zureick A. First Aid for the USMLE Step 1 2018. McGraw-Hill Medical ; 2017
  16. Tao Le, Vikas Bhushan, Deol M, Reyes G. First Aid for the USMLE Step 2 CK, Tenth Edition. McGraw-Hill Education ; 2018
  17. Dihydrorhodamine (DHR) Flow Cytometric Phorbol Myristate Acetate (PMA) Test, Blood. https://www.mayomedicallaboratories.com/test-catalog/Overview/62765. Updated: January 1, 2018. Accessed: July 19, 2018.
  18. Le T, Bhushan V. First Aid for the USMLE Step 1 2015. McGraw-Hill Education ; 2014
  19. Oliveira JB, Fleisher TA. Laboratory evaluation of primary immunodeficiencies. J Allergy Clin Immunol.. 2009; 125 (2): p.297–305. doi: 10.1016/j.jaci.2009.08.043 . | Open in Read by QxMD
  20. Ram S, Lewis LA, Rice PA. Infections of people with complement deficiencies and patients who have undergone splenectomy. Clin Microbiol Rev. 2010; 23 (4): p.740-780. doi: 10.1128/cmr.00048-09 . | Open in Read by QxMD
  21. S. Reis E, Falcao DA, Isaac L. Clinical aspects and molecular basis of primary deficiencies of complement component C3 and its regulatory proteins factor I and factor H. Scand J Immunol. 2006; 63 (3): p.155-168. doi: 10.1111/j.1365-3083.2006.01729.x . | Open in Read by QxMD
  22. Yel L . Selective IgA deficiency. J Clin Immunol. 2010; 30 (1): p.1-16. doi: 10.1007/s10875-009-9357-x . | Open in Read by QxMD
  23. Selective IgA Deficiency. http://www.msdmanuals.com/professional/immunology-allergic-disorders/immunodeficiency-disorders/selective-iga-deficiency. Updated: August 1, 2016. Accessed: May 15, 2017.
  24. Azizi G, Ziaee V, Tavakol M, et al. Approach to the management of autoimmunity in primary immunodeficiency. Scand J Immunol. 2017; 85 (1): p.13-29. doi: 10.1111/sji.12506 . | Open in Read by QxMD
  25. Coombs C, Kirk AS. Oski's Pediatric Certification and Recertification Board Review. Lippincott Williams & Wilkins ; 2011
  26. Bruton Agammaglobulinemia.
  27. Cunningham-Rundles C. The many faces of common variable immunodeficiency. Hematology Am Soc Hematol Educ Program. 2012; 2012 : p.301-305.
  28. Sneller MC. New insights into common variable immunodeficiency. Ann Intern Med. 1993; 118 (9): p.720. doi: 10.7326/0003-4819-118-9-199305010-00011 . | Open in Read by QxMD
  29. Ataxia-telangiectasia. https://ghr.nlm.nih.gov/condition/ataxia-telangiectasia#diagnosis. Updated: April 30, 2019. Accessed: May 9, 2019.
  30. Cole LA. False Positive hCG Assays. Elsevier ; 2010 : p. 229-236
  31. Common Variable Immune Deficiency. https://rarediseases.org/rare-diseases/common-variable-immune-deficiency/. Updated: January 1, 2017. Accessed: April 17, 2020.
  32. Tam JS, Routes JM. Common Variable Immunodeficiency. American Journal of Rhinology & Allergy. 2013; 27 (4): p.260-265. doi: 10.2500/ajra.2013.27.3899 . | Open in Read by QxMD
  33. Macedo ACL, Isaac L. Systemic Lupus Erythematosus and Deficiencies of Early Components of the Complement Classical Pathway. Frontiers in Immunology. 2016; 7 . doi: 10.3389/fimmu.2016.00055 . | Open in Read by QxMD