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Activated PI3K-delta syndrome

MedGen UID:: 978173
•Concept ID:: CN295305
•: Disease or Syndrome

Synonyms:	activated PI3K-delta syndrome; APDS; Senescent T-cells-lymphadenopathy-immunodeficiency syndrome due to p110delta-activating mutation; senescent T-cells-lymphadenopathy-immunodeficiency syndrome due to p110delta-activating mutation
Modes of inheritance:	Autosomal dominant inheritance MedGen UID: 141047 •Concept ID: C0443147 • Intellectual Product Source: Orphanet A mode of inheritance that is observed for traits related to a gene encoded on one of the autosomes (i.e., the human chromosomes 1-22) in which a trait manifests in heterozygotes. In the context of medical genetics, an autosomal dominant disorder is caused when a single copy of the mutant allele is present. Males and females are affected equally, and can both transmit the disorder with a risk of 50% for each child of inheriting the mutant allele. Autosomal dominant inheritance (Orphanet)

Related genes: Gene(s) associated with related conditions. For conditions in a hierarchy, the parent condition will list the genes associated with the children conditions.	PIK3R1, PIK3CD

Monarch Initiative:	MONDO:0018338
Orphanet:	ORPHA397596

Definition

Autosomal dominant immunodeficiency-14A with lymphoproliferation (IMD14A) is a primary immunodeficiency characterized by onset of recurrent sinopulmonary and other infections in early childhood. Laboratory studies show defects in both B- and T-cell populations, with an inability to control infection with Epstein Barr-virus (EBV) and cytomegalovirus (CMV). Patient CD8+ T cells are skewed toward differentiation and senescence. Many patients develop lymphadenopathy, mucosal lymphoid aggregates, and/or increased serum IgM. There is also an increased susceptibility to B-cell lymphomas (summary by Lucas et al., 2014). [from OMIM]

Term Hierarchy

GTR
MeSH

CClinical test, RResearch test, OOMIM, GGeneReviews, VClinVar

CROGVActivated PI3K-delta syndrome
- CROGVImmunodeficiency 14
- CROGVImmunodeficiency 36

Disease
- Disorder by Site
  - Hematopoietic and Lymphoid System Disorder
    - Hematologic disorder
      - Blood Protein Disorders
        Agammaglobulinemia
        Activated PI3K-delta syndrome
        Immunodeficiency 14
        Immunodeficiency 36

Professional guidelines

PubMed

The Treatment of Activated PI3Kδ Syndrome.

Coulter TI, Cant AJ
Front Immunol 2018;9:2043. Epub 2018 Sep 7 doi: 10.3389/fimmu.2018.02043. PMID: 30245694 Free PMC Article

Precision treatment with sirolimus in a case of activated phosphoinositide 3-kinase δ syndrome.

Rae W, Ramakrishnan KA, Gao Y, Ashton-Key M, Pengelly RJ, Patel SV, Ennis S, Williams AP, Faust SN
Clin Immunol 2016 Oct;171:38-40. Epub 2016 Jul 19 doi: 10.1016/j.clim.2016.07.017. PMID: 27444043

See all (2)

Recent clinical studies

Etiology

AKT Hyperphosphorylation and T Cell Exhaustion in Down Syndrome.

Peeters D, Pico-Knijnenburg I, Wieringa D, Rad M, Cuperus R, Ruige M, Froeling F, Zijp GW, van der Burg M, Driessen GJA
Front Immunol 2022;13:724436. Epub 2022 Feb 10 doi: 10.3389/fimmu.2022.724436. PMID: 35222360 Free PMC Article

International retrospective study of allogeneic hematopoietic cell transplantation for activated PI3K-delta syndrome.

Dimitrova D, Nademi Z, Maccari ME, Ehl S, Uzel G, Tomoda T, Okano T, Imai K, Carpenter B, Ip W, Rao K, Worth AJJ, Laberko A, Mukhina A, Néven B, Moshous D, Speckmann C, Warnatz K, Wehr C, Abolhassani H, Aghamohammadi A, Bleesing JJ, Dara J, Dvorak CC, Ghosh S, Kang HJ, Markelj G, Modi A, Bayer DK, Notarangelo LD, Schulz A, Garcia-Prat M, Soler-Palacín P, Karakükcü M, Yilmaz E, Gambineri E, Menconi M, Masmas TN, Holm M, Bonfim C, Prando C, Hughes S, Jolles S, Morris EC, Kapoor N, Koltan S, Paneesha S, Steward C, Wynn R, Duffner U, Gennery AR, Lankester AC, Slatter M, Kanakry JA
J Allergy Clin Immunol 2022 Jan;149(1):410-421.e7. Epub 2021 May 24 doi: 10.1016/j.jaci.2021.04.036. PMID: 34033842 Free PMC Article

Autoimmune Cytopenias and Dysregulated Immunophenotype Act as Warning Signs of Inborn Errors of Immunity: Results From a Prospective Study.

Schiavo E, Martini B, Attardi E, Consonni F, Ciullini Mannurita S, Coniglio ML, Tellini M, Chiocca E, Fotzi I, Luti L, D'Alba I, Veltroni M, Favre C, Gambineri E
Front Immunol 2021;12:790455. Epub 2022 Jan 4 doi: 10.3389/fimmu.2021.790455. PMID: 35058929 Free PMC Article

Update on Infections in Primary Antibody Deficiencies.

Demirdag YY, Gupta S
Front Immunol 2021;12:634181. Epub 2021 Feb 11 doi: 10.3389/fimmu.2021.634181. PMID: 33643318 Free PMC Article

Report of a Chinese Cohort with Activated Phosphoinositide 3-Kinase δ Syndrome.

Wang Y, Wang W, Liu L, Hou J, Ying W, Hui X, Zhou Q, Liu D, Yao H, Sun J, Wang X
J Clin Immunol 2018 Nov;38(8):854-863. Epub 2018 Nov 29 doi: 10.1007/s10875-018-0568-x. PMID: 30499059

See all (8)

Diagnosis

Activated Phosphoinositide 3-Kinase δ Syndrome: a Large Pediatric Cohort from a Single Center in China.

Qiu L, Wang Y, Tang W, Yang Q, Zeng T, Chen J, Chen X, Zhang L, Zhou L, Zhang Z, An Y, Tang X, Zhao X
J Clin Immunol 2022 May;42(4):837-850. Epub 2022 Mar 16 doi: 10.1007/s10875-022-01218-4. PMID: 35296988

Infections in activated PI3K delta syndrome (APDS).

Brodsky NN, Lucas CL
Curr Opin Immunol 2021 Oct;72:146-157. Epub 2021 May 27 doi: 10.1016/j.coi.2021.04.010. PMID: 34052541

Activated PI3K-delta syndrome in an Egyptian pediatric cohort with primary immune deficiency.

Ahmed AA, El Shahaway AA, Hussien SA
Allergol Immunopathol (Madr) 2020 Nov-Dec;48(6):686-693. Epub 2020 Apr 27 doi: 10.1016/j.aller.2019.12.006. PMID: 32349894

Clinical, Immunological, and Genetic Features in Patients with Activated PI3Kδ Syndrome (APDS): a Systematic Review.

Jamee M, Moniri S, Zaki-Dizaji M, Olbrich P, Yazdani R, Jadidi-Niaragh F, Aghamahdi F, Abolhassani H, Condliffe AM, Aghamohammadi A, Azizi G
Clin Rev Allergy Immunol 2020 Dec;59(3):323-333. doi: 10.1007/s12016-019-08738-9. PMID: 31111319

The Treatment of Activated PI3Kδ Syndrome.

Coulter TI, Cant AJ
Front Immunol 2018;9:2043. Epub 2018 Sep 7 doi: 10.3389/fimmu.2018.02043. PMID: 30245694 Free PMC Article

See all (29)

Therapy

Activated Phosphoinositide 3-Kinase δ Syndrome: a Large Pediatric Cohort from a Single Center in China.

The Treatment of Activated PI3Kδ Syndrome.

Coulter TI, Cant AJ
Front Immunol 2018;9:2043. Epub 2018 Sep 7 doi: 10.3389/fimmu.2018.02043. PMID: 30245694 Free PMC Article

Herpesviruses in the Activated Phosphatidylinositol-3-Kinase-δ Syndrome.

Cohen JI
Front Immunol 2018;9:237. Epub 2018 Feb 23 doi: 10.3389/fimmu.2018.00237. PMID: 29599765 Free PMC Article

Activated PI3 Kinase Delta Syndrome: From Genetics to Therapy.

Michalovich D, Nejentsev S
Front Immunol 2018;9:369. Epub 2018 Feb 27 doi: 10.3389/fimmu.2018.00369. PMID: 29535736 Free PMC Article

Effective "activated PI3Kδ syndrome"-targeted therapy with the PI3Kδ inhibitor leniolisib.

Rao VK, Webster S, Dalm VASH, Šedivá A, van Hagen PM, Holland S, Rosenzweig SD, Christ AD, Sloth B, Cabanski M, Joshi AD, de Buck S, Doucet J, Guerini D, Kalis C, Pylvaenaeinen I, Soldermann N, Kashyap A, Uzel G, Lenardo MJ, Patel DD, Lucas CL, Burkhart C
Blood 2017 Nov 23;130(21):2307-2316. Epub 2017 Sep 29 doi: 10.1182/blood-2017-08-801191. PMID: 28972011 Free PMC Article

See all (23)

Prognosis

Systematic review of mortality and survival rates for APDS.

Hanson J, Bonnen PE
Clin Exp Med 2024 Jan 27;24(1):17. doi: 10.1007/s10238-023-01259-y. PMID: 38280023 Free PMC Article

Activated Phosphoinositide 3-Kinase δ Syndrome: a Large Pediatric Cohort from a Single Center in China.

Autoimmune Cytopenia as an Early and Initial Presenting Manifestation in Activated PI3 Kinase Delta Syndrome: Case Report and Review.

Schworer SA, Francis OL, Johnson SM, Smith BD, Gold SH, Smitherman AB, Wu EY
J Pediatr Hematol Oncol 2021 Nov 1;43(8):281-287. doi: 10.1097/MPH.0000000000002214. PMID: 34054047 Free PMC Article

Update on Infections in Primary Antibody Deficiencies.

Demirdag YY, Gupta S
Front Immunol 2021;12:634181. Epub 2021 Feb 11 doi: 10.3389/fimmu.2021.634181. PMID: 33643318 Free PMC Article

Hematopoietic stem cell transplantation for progressive combined immunodeficiency and lymphoproliferation in patients with activated phosphatidylinositol-3-OH kinase δ syndrome type 1.

Okano T, Imai K, Tsujita Y, Mitsuiki N, Yoshida K, Kamae C, Honma K, Mitsui-Sekinaka K, Sekinaka Y, Kato T, Hanabusa K, Endo E, Takashima T, Hiroki H, Yeh TW, Tanaka K, Nagahori M, Tsuge I, Bando Y, Iwasaki F, Shikama Y, Inoue M, Kimoto T, Moriguchi N, Yuza Y, Kaneko T, Suzuki K, Matsubara T, Maruo Y, Kunitsu T, Waragai T, Sano H, Hashimoto Y, Tasaki K, Suzuki O, Shirakawa T, Kato M, Uchiyama T, Ishimura M, Tauchi T, Yagasaki H, Jou ST, Yu HH, Kanegane H, Kracker S, Durandy A, Kojima D, Muramatsu H, Wada T, Inoue Y, Takada H, Kojima S, Ogawa S, Ohara O, Nonoyama S, Morio T
J Allergy Clin Immunol 2019 Jan;143(1):266-275. Epub 2018 May 18 doi: 10.1016/j.jaci.2018.04.032. PMID: 29778502

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Clinical prediction guides

AKT Hyperphosphorylation and T Cell Exhaustion in Down Syndrome.

Dysregulated PI3K Signaling in B Cells of CVID Patients.

Harder I, Münchhalfen M, Andrieux G, Boerries M, Grimbacher B, Eibel H, Maccari ME, Ehl S, Wienands J, Jellusova J, Warnatz K, Keller B
Cells 2022 Jan 28;11(3) doi: 10.3390/cells11030464. PMID: 35159274 Free PMC Article

Genetic Defects in Phosphoinositide 3-Kinase δ Influence CD8(+) T Cell Survival, Differentiation, and Function.

Cannons JL, Preite S, Kapnick SM, Uzel G, Schwartzberg PL
Front Immunol 2018;9:1758. Epub 2018 Aug 2 doi: 10.3389/fimmu.2018.01758. PMID: 30116245 Free PMC Article

Respiratory Manifestations of the Activated Phosphoinositide 3-Kinase Delta Syndrome.

Condliffe AM, Chandra A
Front Immunol 2018;9:338. Epub 2018 Mar 5 doi: 10.3389/fimmu.2018.00338. PMID: 29556229 Free PMC Article

Effective "activated PI3Kδ syndrome"-targeted therapy with the PI3Kδ inhibitor leniolisib.

See all (12)