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Immunodeficiency 14(IMD14A)

MedGen UID:
811535
Concept ID:
C3714976
Disease or Syndrome
Synonyms: IMD14A; IMMUNODEFICIENCY 14A WITH LYMPHOPROLIFERATION, AUTOSOMAL DOMINANT; p110-DELTA-ACTIVATING MUTATION CAUSING SENESCENT T CELLS, LYMPHADENOPATHY, AND IMMUNODEFICIENCY
SNOMED CT: Immunodeficiency 14 (711480000); Activated PI3K-delta syndrome (711480000); p110-delta-activating mutation causing senescent T cells, lymphadenopathy and immunodeficiency (711480000); Activated phosphoinositide 3-kinase delta syndrome (711480000); APDS - activated PI3K-delta syndrome (711480000); PASLI - p110-delta-activating mutation causing senescent T cells, lymphadenopathy, and immunodeficiency (711480000)
 
Gene (location): PIK3CD (1p36.22)
 
Monarch Initiative: MONDO:0014222
OMIM®: 615513

Definition

Activated PI3K-delta syndrome (also known as APDS) is a disorder that impairs the immune system. Individuals with this condition often have low numbers of white blood cells (lymphopenia), particularly B cells and T cells. Normally, these cells recognize and attack foreign invaders, such as viruses and bacteria, to prevent infection. The severity of activated PI3K-delta syndrome varies widely. Some people may have multiple, severe infections while others show mild symptoms to none at all.

Most commonly, people with activated PI3K-delta syndrome develop recurrent infections that begin in childhood, particularly in the lungs, sinuses, and ears. Over time, recurrent respiratory tract infections can lead to a condition called bronchiectasis, which damages the passages leading from the windpipe to the lungs (bronchi) and can cause breathing problems. People with activated PI3K-delta syndrome may also have chronic active viral infections, such as Epstein-Barr virus, herpes simplex virus, or cytomegalovirus infections.

Another possible feature of activated PI3K-delta syndrome is abnormal clumping of white blood cells. These clumps can lead to enlarged lymph nodes (lymphadenopathy) or an enlarged spleen (splenomegaly). The white blood cells can also build up to form solid masses (nodular lymphoid hyperplasia), usually in the moist lining of the airways or intestines. While nodular lymphoid hyperplasia is not cancerous (benign), activated PI3K-delta syndrome increases the risk of developing forms of blood cancer called Hodgkin lymphoma and non-Hodgkin lymphoma.

There are two types of activated PI3K-delta syndrome, each with different genetic causes.

Some people with activated PI3K-delta syndrome develop autoimmunity, which occurs when the body attacks its own tissues and organs by mistake. [from MedlinePlus Genetics]

Clinical features

From HPO
Cellulitis
MedGen UID:
40174
Concept ID:
C0007642
Disease or Syndrome
A bacterial infection and inflammation of the skin und subcutaneous tissues.
Bronchiectasis
MedGen UID:
14234
Concept ID:
C0006267
Disease or Syndrome
Persistent abnormal dilatation of the bronchi owing to localized and irreversible destruction and widening of the large airways.
Recurrent sinopulmonary infections
MedGen UID:
339549
Concept ID:
C1846546
Finding
An increased susceptibility to infections involving both the paranasal sinuses and the lungs, as manifested by a history of recurrent sinopulmonary infections.
Recurrent respiratory infections
MedGen UID:
812812
Concept ID:
C3806482
Finding
An increased susceptibility to respiratory infections as manifested by a history of recurrent respiratory infections.
Immunodeficiency
MedGen UID:
7034
Concept ID:
C0021051
Disease or Syndrome
Failure of the immune system to protect the body adequately from infection, due to the absence or insufficiency of some component process or substance.
Splenomegaly
MedGen UID:
52469
Concept ID:
C0038002
Finding
Abnormal increased size of the spleen.
Lymphadenopathy
MedGen UID:
96929
Concept ID:
C0497156
Disease or Syndrome
Enlargement (swelling) of a lymph node.
Recurrent ear infections
MedGen UID:
473277
Concept ID:
C0743360
Finding
Increased susceptibility to ear infections, as manifested by recurrent episodes of ear infections.
Increased circulating IgM level
MedGen UID:
333454
Concept ID:
C1839972
Finding
An abnormally increased level of immunoglobulin M in blood.
T lymphocytopenia
MedGen UID:
419385
Concept ID:
C2931322
Finding
An abnormally low count of T cells.
Decreased circulating IgG2 concentration
MedGen UID:
867187
Concept ID:
C4021545
Finding
A reduction in immunoglobulin levels of the IgG2 subclass in the blood circulation.
Decreased specific pneumococcal antibody level
MedGen UID:
868496
Concept ID:
C4022890
Finding
The presence of normal overall immunoglobulin levels with deficiency of specific immunoglobulins directed against pneumococci.
Increased proportion of transitional B cells
MedGen UID:
892766
Concept ID:
C4072920
Finding
An elevation in the normal proportion of transitional B cells (CD19+/CD38high/IgMhigh) in circulation relative to the total number of B cells. B cells originate from precursors in the bone marrow, and the first cells which migrate to the peripheral blood have been classified as transitional B cells.
Decreased proportion of class-switched memory B cells
MedGen UID:
892709
Concept ID:
C4072925
Finding
A reduction in the normal proportion of class-switched memory B cells (CD19+/CD27+/IgM+/IgD+) relative to the total number of B cells. Marginal zone B cells undergo limited somatic hypermutation and produce high-affinity IgM and some IgG, whereas class-switched memory B cells synthetize IgG, IgM, and IgA.

Professional guidelines

PubMed

Aghamohammadi A, Mohammadinejad P, Abolhassani H, Mirminachi B, Movahedi M, Gharagozlou M, Parvaneh N, Zeiaee V, Mirsaeed-Ghazi B, Chavoushzadeh Z, Mahdaviani A, Mansouri M, Yousefzadegan S, Sharifi B, Zandieh F, Hedayat E, Nadjafi A, Sherkat R, Shakerian B, Sadeghi-Shabestari M, Hosseini RF, Jabbari-Azad F, Ahanchian H, Behmanesh F, Zandkarimi M, Shirkani A, Cheraghi T, Fayezi A, Mohammadzadeh I, Amin R, Aleyasin S, Moghtaderi M, Ghaffari J, Arshi S, Javahertrash N, Nabavi M, Bemanian MH, Shafiei A, Kalantari N, Ahmadiafshar A, Khazaei HA, Atarod L, Rezaei N
J Clin Immunol 2014 May;34(4):478-90. doi: 10.1007/s10875-014-0001-z. PMID: 24659230

Recent clinical studies

Etiology

Bauhofer A, Balaban Ü, Schimo S, Mayer M, Schüttrumpf J, Borte S
Int J Clin Pharmacol Ther 2024 Oct;62(10):448-459. doi: 10.5414/CP204595. PMID: 39078054Free PMC Article
Wang H, Xu BP, Bao YM, Yang Y, Qian LL, Zhang HL, Zhu CM, Yin Y, Jiang M, Dai JH, Xu YS, Zhu XH, Zhu XP, Shen KL
Clin Respir J 2023 Sep;17(9):841-850. Epub 2023 May 31 doi: 10.1111/crj.13630. PMID: 37259267Free PMC Article
Miglani A, Divekar RD, Azar A, Rank MA, Lal D
Int Forum Allergy Rhinol 2018 Sep;8(9):1047-1051. Epub 2018 May 31 doi: 10.1002/alr.22146. PMID: 29851243
Aghamohammadi A, Mohammadinejad P, Abolhassani H, Mirminachi B, Movahedi M, Gharagozlou M, Parvaneh N, Zeiaee V, Mirsaeed-Ghazi B, Chavoushzadeh Z, Mahdaviani A, Mansouri M, Yousefzadegan S, Sharifi B, Zandieh F, Hedayat E, Nadjafi A, Sherkat R, Shakerian B, Sadeghi-Shabestari M, Hosseini RF, Jabbari-Azad F, Ahanchian H, Behmanesh F, Zandkarimi M, Shirkani A, Cheraghi T, Fayezi A, Mohammadzadeh I, Amin R, Aleyasin S, Moghtaderi M, Ghaffari J, Arshi S, Javahertrash N, Nabavi M, Bemanian MH, Shafiei A, Kalantari N, Ahmadiafshar A, Khazaei HA, Atarod L, Rezaei N
J Clin Immunol 2014 May;34(4):478-90. doi: 10.1007/s10875-014-0001-z. PMID: 24659230

Diagnosis

Wang H, Xu BP, Bao YM, Yang Y, Qian LL, Zhang HL, Zhu CM, Yin Y, Jiang M, Dai JH, Xu YS, Zhu XH, Zhu XP, Shen KL
Clin Respir J 2023 Sep;17(9):841-850. Epub 2023 May 31 doi: 10.1111/crj.13630. PMID: 37259267Free PMC Article
Aghamohammadi A, Mohammadinejad P, Abolhassani H, Mirminachi B, Movahedi M, Gharagozlou M, Parvaneh N, Zeiaee V, Mirsaeed-Ghazi B, Chavoushzadeh Z, Mahdaviani A, Mansouri M, Yousefzadegan S, Sharifi B, Zandieh F, Hedayat E, Nadjafi A, Sherkat R, Shakerian B, Sadeghi-Shabestari M, Hosseini RF, Jabbari-Azad F, Ahanchian H, Behmanesh F, Zandkarimi M, Shirkani A, Cheraghi T, Fayezi A, Mohammadzadeh I, Amin R, Aleyasin S, Moghtaderi M, Ghaffari J, Arshi S, Javahertrash N, Nabavi M, Bemanian MH, Shafiei A, Kalantari N, Ahmadiafshar A, Khazaei HA, Atarod L, Rezaei N
J Clin Immunol 2014 May;34(4):478-90. doi: 10.1007/s10875-014-0001-z. PMID: 24659230

Therapy

Bauhofer A, Balaban Ü, Schimo S, Mayer M, Schüttrumpf J, Borte S
Int J Clin Pharmacol Ther 2024 Oct;62(10):448-459. doi: 10.5414/CP204595. PMID: 39078054Free PMC Article

Prognosis

Miglani A, Divekar RD, Azar A, Rank MA, Lal D
Int Forum Allergy Rhinol 2018 Sep;8(9):1047-1051. Epub 2018 May 31 doi: 10.1002/alr.22146. PMID: 29851243

Clinical prediction guides

Miglani A, Divekar RD, Azar A, Rank MA, Lal D
Int Forum Allergy Rhinol 2018 Sep;8(9):1047-1051. Epub 2018 May 31 doi: 10.1002/alr.22146. PMID: 29851243

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