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Dysgammaglobulinemia

MedGen UID:
41679
Concept ID:
C0013374
Disease or Syndrome
Synonym: Dysgammaglobulinemias
SNOMED CT: Dysgammaglobulinemia (123782009)
 
HPO: HP:0002961
Monarch Initiative: MONDO:0001342

Definition

Selective deficiency of one or more, but not all, classes of immunoglobulins. [from HPO]

Conditions with this feature

Hyper-IgM syndrome type 1
MedGen UID:
96019
Concept ID:
C0398689
Disease or Syndrome
X-linked hyper IgM syndrome (HIGM1), a disorder of abnormal T- and B-cell function, is characterized by low serum concentrations of IgG, IgA, and IgE with normal or elevated serum concentrations of IgM. Mitogen proliferation may be normal, but NK- and T-cell cytotoxicity can be impaired. Antigen-specific responses are usually decreased or absent. Total numbers of B cells are normal but there is a marked reduction of class-switched memory B cells. Defective oxidative burst of both neutrophils and macrophages has been reported. The range of clinical findings varies, even within the same family. More than 50% of males with HIGM1 develop symptoms by age one year, and more than 90% are symptomatic by age four years. HIGM1 usually presents in infancy with recurrent upper- and lower-respiratory tract bacterial infections, opportunistic infections including Pneumocystis jirovecii pneumonia, and recurrent or protracted diarrhea that can be infectious or noninfectious and is associated with failure to thrive. Neutropenia is common; thrombocytopenia and anemia are less commonly seen. Autoimmune and/or inflammatory disorders (such as sclerosing cholangitis) as well as increased risk for neoplasms have been reported as medical complications of this disorder. Significant neurologic complications, often the result of a CNS infection, are seen in 5%-15% of affected males. Liver disease, a serious complication of HIGM1 once observed in more than 80% of affected males by age 20 years, may be decreasing with adequate screening and treatment of Cryptosporidium infection.
Microcephaly, normal intelligence and immunodeficiency
MedGen UID:
140771
Concept ID:
C0398791
Disease or Syndrome
Nijmegen breakage syndrome (NBS) is characterized by progressive microcephaly, early growth deficiency that improves with age, recurrent respiratory infections, an increased risk for malignancy (primarily lymphoma), and premature ovarian failure in females. Developmental milestones are attained at the usual time during the first year; however, borderline delays in development and hyperactivity may be observed in early childhood. Intellectual abilities tend to decline over time. Recurrent pneumonia and bronchitis may result in respiratory failure and early death. Other reported malignancies include solid tumors (e.g., medulloblastoma, glioma, rhabdomyosarcoma).
Ectodermal dysplasia and immunodeficiency 1
MedGen UID:
375787
Concept ID:
C1846008
Disease or Syndrome
Ectodermal dysplasia with immunodeficiency-1 (EDAID1) is an X-linked recessive disorder that characteristically affects only males. Affected individuals have onset of recurrent severe infections due to immunodeficiency in early infancy or in the first years of life. There is increased susceptibility to bacterial, pneumococcal, mycobacterial, and fungal infections. Laboratory studies usually show dysgammaglobulinemia with low IgG subsets and normal or increased IgA and IgM, consistent with impaired 'class-switching' of B cells, although immunologic abnormalities may be subtle compared to the clinical picture, and B- and T-cell numbers are usually normal. There is a poor antibody response to polysaccharide vaccinations, particularly pneumococcus; response to other vaccinations is variable. Patients also have features of ectodermal dysplasia, including conical incisors, hypo/anhidrosis, and thin skin or hair. Severely affected individuals may also show lymphedema, osteopetrosis, and, rarely, hematologic abnormalities. The phenotype is highly variable, likely due to different hypomorphic mutations, and may be fatal in childhood. Intravenous immunoglobulins and prophylactic antibiotics are used as treatment; some patients may benefit from bone marrow transplantation. Although only males tend to be affected with immunodeficiency, many patients inherit a mutation from a mother who has mild features of IP or conical teeth (summary by Doffinger et al., 2001, Orange et al., 2004, Roberts et al., 2010, Heller et al., 2020). Genetic Heterogeneity of Ectodermal Dysplasia and Immune Deficiency Also see EDAID2 (612132), caused by mutation in the NFKBIA gene (164008).
X-linked lymphoproliferative disease due to SH2D1A deficiency
MedGen UID:
1770239
Concept ID:
C5399825
Disease or Syndrome
X-linked lymphoproliferative disease (XLP) has two recognizable subtypes, XLP1 and XLP2. XLP1 is characterized predominantly by one of three commonly recognized phenotypes: Inappropriate immune response to Epstein-Barr virus (EBV) infection leading to hemophagocytic lymphohistiocytosis (HLH) or severe mononucleosis. Dysgammaglobulinemia. Lymphoproliferative disease (malignant lymphoma). XLP2 is most often characterized by HLH (often associated with EBV), dysgammaglobulinemia, and inflammatory bowel disease. HLH resulting from EBV infection is associated with an unregulated and exaggerated immune response with widespread proliferation of cytotoxic T cells, EBV-infected B cells, and macrophages. Dysgammaglobulinemia is typically hypogammaglobulinemia of one or more immunoglobulin subclasses. The malignant lymphomas are typically B-cell lymphomas, non-Hodgkin type, often extranodal, and in particular involving the intestine.

Professional guidelines

PubMed

Shadur B, Abuzaitoun O, NaserEddin A, Even-Or E, Zaidman I, Stepensky P
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Recent clinical studies

Etiology

Ghosh S, Bienemann K, Boztug K, Borkhardt A
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Matthew DJ, Taylor B, Norman AP, Turner MW
Lancet 1977 Feb 12;1(8007):321-4. doi: 10.1016/s0140-6736(77)91131-x. PMID: 64855

Diagnosis

Tragiannidis A, Groll AH
Paediatr Drugs 2021 Sep;23(5):445-455. Epub 2021 Jul 22 doi: 10.1007/s40272-021-00461-3. PMID: 34292515
Panchabhai TS, Farver C, Highland KB
Clin Chest Med 2016 Sep;37(3):463-74. Epub 2016 Jun 25 doi: 10.1016/j.ccm.2016.04.009. PMID: 27514593
Wall LA, Dimitriades VR, Sorensen RU
Immunol Allergy Clin North Am 2015 Nov;35(4):659-70. Epub 2015 Aug 25 doi: 10.1016/j.iac.2015.07.003. PMID: 26454312
Smith TF
Adv Pediatr 1992;39:101-26. PMID: 1442311
Fisher CH, Oh KS, Bayless TM, Siegelman SS
Am J Roentgenol Radium Ther Nucl Med 1975 Sep;125(1):207-17. doi: 10.2214/ajr.125.1.207. PMID: 1106221

Therapy

Tragiannidis A, Groll AH
Paediatr Drugs 2021 Sep;23(5):445-455. Epub 2021 Jul 22 doi: 10.1007/s40272-021-00461-3. PMID: 34292515
Panchabhai TS, Farver C, Highland KB
Clin Chest Med 2016 Sep;37(3):463-74. Epub 2016 Jun 25 doi: 10.1016/j.ccm.2016.04.009. PMID: 27514593
Shapiro GG
J Allergy Clin Immunol 1988 May;81(5 Pt 2):1025-7. doi: 10.1016/0091-6749(88)90173-x. PMID: 3286728
Aarli JA
Springer Semin Immunopathol 1985;8(1-2):5-28. doi: 10.1007/BF00197244. PMID: 2408350
Fisher CH, Oh KS, Bayless TM, Siegelman SS
Am J Roentgenol Radium Ther Nucl Med 1975 Sep;125(1):207-17. doi: 10.2214/ajr.125.1.207. PMID: 1106221

Prognosis

Tragiannidis A, Groll AH
Paediatr Drugs 2021 Sep;23(5):445-455. Epub 2021 Jul 22 doi: 10.1007/s40272-021-00461-3. PMID: 34292515
Deyà-Martínez A, Gordón Y, Molina-Anguita C, Vlagea A, Piquer M, Juan M, Esteve-Solé A, Antón J, Madrid Á, García-García A, Plaza AM, Armangue T, Alsina L
Neurol Neuroimmunol Neuroinflamm 2020 Jul;7(4) Epub 2020 May 6 doi: 10.1212/NXI.0000000000000724. PMID: 32376706Free PMC Article
Wall LA, Dimitriades VR, Sorensen RU
Immunol Allergy Clin North Am 2015 Nov;35(4):659-70. Epub 2015 Aug 25 doi: 10.1016/j.iac.2015.07.003. PMID: 26454312
Shapiro GG
J Allergy Clin Immunol 1988 May;81(5 Pt 2):1025-7. doi: 10.1016/0091-6749(88)90173-x. PMID: 3286728
Waldenström JG
Acta Med Scand 1984;216(5):435-47. doi: 10.1111/j.0954-6820.1984.tb05032.x. PMID: 6441456

Clinical prediction guides

Nishida N, Yang X, Takasaki I, Imai K, Kato K, Inoue Y, Imamura T, Miyashita R, Kato F, Yamaide A, Mori M, Saito S, Hara J, Adachi Y, Miyawaki T, Kanegane H
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Louis AG, Gupta S
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Elamin I, Edwards MJ, Martino D
Behav Neurol 2013;27(1):23-32. doi: 10.3233/BEN-120295. PMID: 23187145Free PMC Article
Waldenström JG
Acta Med Scand 1984;216(5):435-47. doi: 10.1111/j.0954-6820.1984.tb05032.x. PMID: 6441456
Boder E
Birth Defects Orig Artic Ser 1975;11(1):255-70. PMID: 1096982

Recent systematic reviews

Schwitzguébel AJ, Jandus P, Lacroix JS, Seebach JD, Harr T
J Allergy Clin Immunol 2015 Dec;136(6):1523-1531. Epub 2015 Aug 29 doi: 10.1016/j.jaci.2015.07.016. PMID: 26329513

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