Information on APDS1

Basic details

Name: Activated p110-delta syndrome 1 | Acronym: APDS1
Alt. names: activated PI3K delta syndrome | Senescent T-cells-lymphadenopathy-immunodeficiency syndrome due to p110delta-GOF | immunodeficiency 14A | IMD14A

Gene: PIK3CD | MOI: Autosomal dominant | Mechanism of action: Gain of Function

No. of cases in DB: 66 | First reported in: 2006

Last updated on: 2023-02-28 16:41:18 by

OMIM: 615513

Orphanet: 397596

MONDO: 0018338

DOID: -

ClinGen:

Description

Activated PI3K-delta syndrome is a rare, genetic, primary immunodeficiency disease characterized by increased susceptibility to recurrent and/or severe bacterial and viral infections (in particular, sinopulmonary bacterial and herpesvirus infections), chronic benign lymphoproliferation (manifesting as lympadenopathy, hepatosplenomegaly and focal nodular lymphoid hyperplasia), and/or autoimmune disease (including immune cytopenias, juvenile arthritis, glomerulonephritis and sclerosing cholangitis). Immunophenotypically, variable degrees of agammaglobulinemia with increased IgM levels, increased circulating transitional B cells, decreased naïve CD4 and CD8 T-cells with increased CD8 effector/memory T cells are observed.

Management

Antiinfectious prophylaxis and early and aggressive treatment of infections may be beneficial. Individuals have been described as developing lymphoma, and awareness may allow early recognition and management.

Please mind that full curation of this condition has not been completed yet. It is currently ongoing.

66 reported cases added to GenIA

SubjectID Sex Fam.ID AD AFM Validity Country Population Reference & Pub.code
101104arrow icon F 211429 17 Germany PMID:34975878 [Fam.F397:P397]
101495arrow icon M 212458 12 Taiwan Taiwanese PMID:16984281 [P3(II.1)]
101501arrow icon F 212459 United Kingdom British PMID:24136356 [Fam.A:II.2(P4)]
101509arrow icon F 212459 United Kingdom British PMID:24136356 [Fam.A:III.2(P1)]
101511arrow icon M 212459 United Kingdom British PMID:24136356 [Fam.A:III.3(P2)]
101512arrow icon M 212459 United Kingdom British PMID:24136356 [Fam.A:III.4(P3)]
101530arrow icon M 212460 United Kingdom British PMID:24136356 [Fam.B:III.3(P5)]
101532arrow icon F 212460 United Kingdom British PMID:24136356 [Fam.B:III.5(P6)]
101534arrow icon M 212460 United Kingdom British PMID:24136356 [Fam.B:IV.1(P11)]
101538arrow icon F 212460 United Kingdom British PMID:24136356 [Fam.B:IV.3(P7)]
101541arrow icon M 212461 United Kingdom Slovenian PMID:24136356 [Fam.C:II.1(P8)]
101546arrow icon F 212462 United Kingdom Irish PMID:24136356 [Fam.D:II.1(P10)]
101548arrow icon M 212462 United Kingdom Irish PMID:24136356 [Fam.D:III.1(P9)]
101549arrow icon F 212463 United Kingdom British PMID:24136356 [Fam.E:I.1(P13)]
101551arrow icon M 212463 United Kingdom British PMID:24136356 [Fam.E:II.1(P12)]
101552arrow icon M 212464 United Kingdom French PMID:24136356 [Fam.F:II.1(P14)]
101560arrow icon M 212465 United Kingdom French PMID:24136356 [Fam.G:II.2(P15)]
101561arrow icon F 212465 United Kingdom French PMID:24136356 [Fam.G:II.3(P16)]
101563arrow icon M 212465 United Kingdom French PMID:24136356 [Fam.G:II.4(P17)]
105481arrow icon M 215777tree icon 12 Haitian/Hispanic PMID:24165795 [Fam.A:II.1(A.1)]
105482arrow icon F 215778tree icon Caucasian PMID:24165795 [Fam.B:I.2(I.2)]
105483arrow icon F 215778tree icon Caucasian PMID:24165795 [Fam.B:II.2(II.2)]
105484arrow icon F 215778tree icon 14 Caucasian PMID:24165795 [Fam.B:III.1(B.III.1)]
105485arrow icon M 215778tree icon Caucasian PMID:24165795 [Fam.B:II.1]
105486arrow icon F 215779tree icon 15 Afro-American PMID:24165795 [Fam.C:II.1(C.1)]
105487arrow icon F 215780tree icon 12 Afro-American PMID:24165795 [Fam.G:II.1(G.1)]
105504arrow icon F 215783tree icon 7 Asian PMID:24165795 [Fam.E:II.1(E.1)]
105507arrow icon M 215784tree icon 40 Caucasian PMID:24165795 [Fam.D:I.1(D.I.1)]
105509arrow icon M 215784tree icon 15 Caucasian PMID:24165795 [Fam.D:II.1(D.II.1)]
105510arrow icon F 215784tree icon 12 Caucasian PMID:24165795 [Fam.D:II.2(D.II.2)]
105513arrow icon F 215787tree icon 17 Caucasian PMID:24165795 [Fam.F:II.1(F.II.1)]
105514arrow icon M 215787tree icon Caucasian PMID:24165795 [Fam.F:I.1(F.I.1)]
105516arrow icon M 215787tree icon Caucasian PMID:24165795 [Fam.F:II.3(F.II.2)]
105537arrow icon M 215793 2 PMID:24698326 [P1]
105568arrow icon M 215809 0 PMID:24698326 [Fam.A:II.1(P2)]
105569arrow icon F 215809 8 PMID:24698326 [Fam.A:II.2(P7)]
105571arrow icon U 215810 2 PMID:24698326 [P3]
105573arrow icon U 215812 8 PMID:24698326 [P4]
105574arrow icon U 215813 5 PMID:24698326 [P5]
105575arrow icon U 215814 4 PMID:24698326 [P6]
105576arrow icon U 215815 2 PMID:24698326 [P8]
105587arrow icon F 215820 19 2 Caucasian PMID:24610295 [Fam.1:II.1(F1P1)]
105591arrow icon F 215821 36 -1 Caucasian PMID:24610295 [Fam.2:II.1(F2P2)]
105609arrow icon M 215821 Caucasian PMID:24610295 [Fam.2:III.1(F2P3)]
105616arrow icon F 215822 34 Caucasian PMID:25352054 [Fam.1:II.4(P1)]
105623arrow icon M 215822 27 2 Caucasian PMID:25352054 [Fam.1:II.6(P2)]
105626arrow icon M 215822 10 1 Caucasian PMID:25352054 [Fam.1:III.1(P3)]
105627arrow icon F 215822 8 Caucasian PMID:25352054 [Fam.1:III.2(P4)]
105628arrow icon F 215822 8 Caucasian PMID:25352054 [Fam.1:III.3(P5)]
105634arrow icon M 215828 6 0 Brasilian PMID:25956317 [P1]
105635arrow icon F 215829 26 1 Caucasian PMID:26371693 [1]
105657arrow icon F 215835 16 3 PMID:27379089 [11]
105658arrow icon M 215836 26 1 PMID:26437962 [Fam.A:II.1(Sibling 1)]
105659arrow icon F 215836 21 1 PMID:26437962 [Fam.A:II.2(Sibling 2)]
105660arrow icon F 215836 20 1 PMID:26437962 [Fam.A:II.3(Sibling 3)]
105827arrow icon M 215884 15 6 Definitive German PMID:26437962 [Fam.Sporadic patien:Sporadic patient 1]
105830arrow icon M 215887 9 3 Definitive Polish PMID:26437962 [Fam.2 Sporadic pati:2 Sporadic patient 2]
105872arrow icon F 215896 Definitive Spain European PMID:32961022 [APDS(I.-)]
106355arrow icon F 215999tree icon 34 7 Definitive United Kingdom British PMID:34922003 [Fam.C:II.1(C1)]
107043arrow icon M 216282 4 4 Definitive United Kingdom PMID:27444043 [P1]
107044arrow icon M 216283 28 Definitive PMID:28983403 [P1]
107045arrow icon M 216284 13 Definitive PMID:28428270 [P1]
107046arrow icon M 216285 10 1 Definitive PMID:28428270 [P2]
107047arrow icon F 216286 9 1 Definitive PMID:28428270 [P3]
107138arrow icon M 216357 10 2 Definitive PMID:28469999 [Patient(II.1)]
107141arrow icon F 216358 56 Definitive European/American PMID:28578023 [Patient]

AD: Age at genetic diagnosis; AFM: age at first manifestation; PMID: PubMed ID; GRID: GenIA reference ID (ref. not in PubMed).

Summary of clinical findings

[Considering only Definitive and Possible cases]

Rank Clinical term Present Absent Unreported
1 (unusual) Respiratory tract infectionarrow icon 54 (81.8%) 0 (0.0%) 12 (18.2%)
2 Abnormal lymphoproliferationarrow icon 43 (65.2%) 0 (0.0%) 23 (34.9%)
3 Increased IgM levelsarrow icon 28 (42.4%) 0 (0.0%) 38 (57.6%)
4 Lung diseasearrow icon 28 (42.4%) 0 (0.0%) 38 (57.6%)
5 Bronchiectasisarrow icon 26 (39.4%) 0 (0.0%) 40 (60.6%)
6 Sinopulmonary infectionsarrow icon 24 (36.4%) 0 (0.0%) 42 (63.6%)
7 Otitis mediaarrow icon 22 (33.3%) 0 (0.0%) 44 (66.7%)
8 Splenomegalyarrow icon 21 (31.8%) 0 (0.0%) 45 (68.2%)
9 Lymphadenopathyarrow icon 20 (30.3%) 0 (0.0%) 46 (69.7%)
10 Reduced number of B cellsarrow icon 20 (30.3%) 0 (0.0%) 46 (69.7%)
11 Decreased proportion of switched memory B cellsarrow icon 19 (28.8%) 0 (0.0%) 47 (71.2%)
12 Increased proportion of transitional B cellsarrow icon 19 (28.8%) 0 (0.0%) 47 (71.2%)
13 Recurrent upper respiratory tract infectionarrow icon 18 (27.3%) 0 (0.0%) 48 (72.7%)
14 Hypogammaglobulinemiaarrow icon 18 (27.3%) 0 (0.0%) 48 (72.7%)
15 Reduced proportion of naive CD4 T cellsarrow icon 13 (19.7%) 0 (0.0%) 53 (80.3%)
16 Reduced T cell countarrow icon 13 (19.7%) 0 (0.0%) 53 (80.3%)
17 Hepatopathyarrow icon 12 (18.2%) 0 (0.0%) 54 (81.8%)
18 (unusual) Viral infectionarrow icon 12 (18.2%) 0 (0.0%) 54 (81.8%)
19 Persistent EBV viremiaarrow icon 12 (18.2%) 0 (0.0%) 54 (81.8%)
20 Decreased IgA levelsarrow icon 11 (16.7%) 0 (0.0%) 55 (83.3%)
21 Reduced IgG2 levelsarrow icon 10 (15.2%) 0 (0.0%) 56 (84.9%)
22 Enteropathyarrow icon 10 (15.2%) 0 (0.0%) 56 (84.9%)
23 Decreased IgG levelsarrow icon 9 (13.6%) 0 (0.0%) 57 (86.4%)
24 Lymphoproliferative disorderarrow icon 9 (13.6%) 0 (0.0%) 57 (86.4%)
25 Reduced ab-response to pneumococcal polysaccharide vaccinearrow icon 9 (13.6%) 0 (0.0%) 57 (86.4%)
26 Reduced proportion of CD4 T cellsarrow icon 9 (13.6%) 0 (0.0%) 57 (86.4%)
27 Hepatosplenomegalyarrow icon 8 (12.1%) 0 (0.0%) 58 (87.9%)
28 Increased proportion of effector mem. CD8 T cellsarrow icon 8 (12.1%) 0 (0.0%) 58 (87.9%)
29 Diarrheaarrow icon 8 (12.1%) 0 (0.0%) 58 (87.9%)
30 Abscessarrow icon 7 (10.6%) 0 (0.0%) 59 (89.4%)
31 Autoimmunityarrow icon 6 (9.1%) 0 (0.0%) 60 (90.9%)
32 Autoimmune cytopeniaarrow icon 6 (9.1%) 0 (0.0%) 60 (90.9%)
33 Herpes Simplex Virus Infectionarrow icon 6 (9.1%) 0 (0.0%) 60 (90.9%)
34 Cytomegalovirus infectionarrow icon 6 (9.1%) 0 (0.0%) 60 (90.9%)
35 Pneumoniaarrow icon 6 (9.1%) 0 (0.0%) 60 (90.9%)
36 Sinusitisarrow icon 5 (7.6%) 0 (0.0%) 61 (92.4%)
37 Reduced NK cell numberarrow icon 5 (7.6%) 0 (0.0%) 61 (92.4%)
38 Decreased proportion of memory B cellsarrow icon 4 (6.1%) 0 (0.0%) 62 (93.9%)
39 Recurrent lower respiratory tract infectionsarrow icon 4 (6.1%) 0 (0.0%) 62 (93.9%)
40 Thrombocytopeniaarrow icon 4 (6.1%) 0 (0.0%) 62 (93.9%)
41 Neutropeniaarrow icon 4 (6.1%) 0 (0.0%) 62 (93.9%)
42 Intestinal lymphoid nodular hyperplasiaarrow icon 4 (6.1%) 0 (0.0%) 62 (93.9%)
43 Cervical lymphadenopathyarrow icon 4 (6.1%) 0 (0.0%) 62 (93.9%)
44 Eczemaarrow icon 4 (6.1%) 0 (0.0%) 62 (93.9%)
45 Skin infections arrow icon 4 (6.1%) 0 (0.0%) 62 (93.9%)
46 Cellulitisarrow icon 3 (4.6%) 0 (0.0%) 63 (95.5%)
47 Diffuse large B-cell lymphomaarrow icon 3 (4.6%) 0 (0.0%) 63 (95.5%)
48 Autoimmune hemolytic anemiaarrow icon 3 (4.6%) 0 (0.0%) 63 (95.5%)
49 Hodgkin lymphomaarrow icon 3 (4.6%) 0 (0.0%) 63 (95.5%)
50 Varicella zoster virus infectionarrow icon 3 (4.6%) 0 (0.0%) 63 (95.5%)
51 Tooth abscessarrow icon 3 (4.6%) 0 (0.0%) 63 (95.5%)
52 Colitisarrow icon 2 (3.0%) 0 (0.0%) 64 (97.0%)
53 Plantar wartsarrow icon 2 (3.0%) 0 (0.0%) 64 (97.0%)
54 Periorbital edemaarrow icon 2 (3.0%) 0 (0.0%) 64 (97.0%)
55 Mucocutaneous candidiasisarrow icon 2 (3.0%) 0 (0.0%) 64 (97.0%)
56 Osteoporosisarrow icon 2 (3.0%) 0 (0.0%) 64 (97.0%)
57 Lymphopeniaarrow icon 2 (3.0%) 0 (0.0%) 64 (97.0%)
58 Septicaemiaarrow icon 2 (3.0%) 0 (0.0%) 64 (97.0%)
59 Malignant neoplasmarrow icon 2 (3.0%) 0 (0.0%) 64 (97.0%)
60 Reduced proportion of CD8 T cellsarrow icon 2 (3.0%) 0 (0.0%) 64 (97.0%)
61 Autoimmune thrombocytopeniaarrow icon 2 (3.0%) 0 (0.0%) 64 (97.0%)
62 Failure to thrivearrow icon 2 (3.0%) 0 (0.0%) 64 (97.0%)
63 Generalized lymphadenopathyarrow icon 2 (3.0%) 0 (0.0%) 64 (97.0%)
64 Increased IgG levelarrow icon 2 (3.0%) 0 (0.0%) 64 (97.0%)
65 Primary sclerosing cholangitisarrow icon 2 (3.0%) 0 (0.0%) 64 (97.0%)
66 Bloody diarrheaarrow icon 2 (3.0%) 0 (0.0%) 64 (97.0%)
67 Macrocephalyarrow icon 1 (1.5%) 0 (0.0%) 65 (98.5%)
68 Chronic otitis mediaarrow icon 1 (1.5%) 0 (0.0%) 65 (98.5%)
69 Decreased proportion of unswitched memory B cellsarrow icon 1 (1.5%) 0 (0.0%) 65 (98.5%)
70 Impaired Ig class switch recombinationarrow icon 1 (1.5%) 0 (0.0%) 65 (98.5%)
71 Norovirus infectionarrow icon 1 (1.5%) 0 (0.0%) 65 (98.5%)
72 Pulmonary sequestrationarrow icon 1 (1.5%) 0 (0.0%) 65 (98.5%)
73 Gastroesophageal refluxarrow icon 1 (1.5%) 0 (0.0%) 65 (98.5%)
74 RSV bronchiolitisarrow icon 1 (1.5%) 0 (0.0%) 65 (98.5%)
75 Nephrolithiasisarrow icon 1 (1.5%) 0 (0.0%) 65 (98.5%)
76 Exocrine pancreatic insufficiencyarrow icon 1 (1.5%) 0 (0.0%) 65 (98.5%)
77 Increased proportion of plasmablastsarrow icon 1 (1.5%) 0 (0.0%) 65 (98.5%)
78 Pharyngitisarrow icon 1 (1.5%) 0 (0.0%) 65 (98.5%)
79 Recurrent feversarrow icon 1 (1.5%) 0 (0.0%) 65 (98.5%)
80 Interstitial lung diseasearrow icon 1 (1.5%) 0 (0.0%) 65 (98.5%)
81 Chronic rhinitisarrow icon 1 (1.5%) 0 (0.0%) 65 (98.5%)
82 short staturearrow icon 1 (1.5%) 0 (0.0%) 65 (98.5%)
83 Recurrent infectionsarrow icon 1 (1.5%) 0 (0.0%) 65 (98.5%)
84 Follicular hyperplasiaarrow icon 1 (1.5%) 0 (0.0%) 65 (98.5%)
85 Lymphadenitisarrow icon 1 (1.5%) 0 (0.0%) 65 (98.5%)
86 Endocrine system abnormalityarrow icon 1 (1.5%) 0 (0.0%) 65 (98.5%)
87 Wartsarrow icon 1 (1.5%) 0 (0.0%) 65 (98.5%)
88 Bacterial meningitisarrow icon 1 (1.5%) 0 (0.0%) 65 (98.5%)
89 Anemiaarrow icon 1 (1.5%) 0 (0.0%) 65 (98.5%)
90 ulcerative colitisarrow icon 1 (1.5%) 0 (0.0%) 65 (98.5%)
91 (unusual) Giardiasisarrow icon 1 (1.5%) 0 (0.0%) 65 (98.5%)
92 Urinary tract infectionarrow icon 1 (1.5%) 0 (0.0%) 65 (98.5%)
93 Conjunctivitisarrow icon 1 (1.5%) 0 (0.0%) 65 (98.5%)
94 Thyroiditisarrow icon 1 (1.5%) 0 (0.0%) 65 (98.5%)
95 Atopyarrow icon 1 (1.5%) 0 (0.0%) 65 (98.5%)
96 Hepatomegalyarrow icon 1 (1.5%) 0 (0.0%) 65 (98.5%)
97 Scoliosisarrow icon 1 (1.5%) 0 (0.0%) 65 (98.5%)
98 Rectal abscessarrow icon 1 (1.5%) 0 (0.0%) 65 (98.5%)
99 Severe recurrent varicellaarrow icon 1 (1.5%) 0 (0.0%) 65 (98.5%)
100 Lymphomaarrow icon 1 (1.5%) 0 (0.0%) 65 (98.5%)
101 Non-Hodgkin lymphomaarrow icon 1 (1.5%) 0 (0.0%) 65 (98.5%)
102 pericarditisarrow icon 1 (1.5%) 0 (0.0%) 65 (98.5%)
103 Pancytopeniaarrow icon 1 (1.5%) 0 (0.0%) 65 (98.5%)
104 Basal cell carcinomaarrow icon 1 (1.5%) 0 (0.0%) 65 (98.5%)
105 Henoch-Schönlein Purpuraarrow icon 1 (1.5%) 0 (0.0%) 65 (98.5%)
106 Synovitisarrow icon 1 (1.5%) 0 (0.0%) 65 (98.5%)
107 Tonsillitisarrow icon 1 (1.5%) 0 (0.0%) 65 (98.5%)
108 Nodular regenerative hyperplasia of liverarrow icon 1 (1.5%) 0 (0.0%) 65 (98.5%)
109 cirrhosisarrow icon 1 (1.5%) 0 (0.0%) 65 (98.5%)
110 cholelithiasisarrow icon 1 (1.5%) 0 (0.0%) 65 (98.5%)
111 MALT lymphomaarrow icon 1 (1.5%) 0 (0.0%) 65 (98.5%)
112 Molluscum contagiosumarrow icon 1 (1.5%) 0 (0.0%) 65 (98.5%)
113 Lymph node abscessarrow icon 1 (1.5%) 0 (0.0%) 65 (98.5%)
114 Increased NK cell numberarrow icon 1 (1.5%) 0 (0.0%) 65 (98.5%)
115 Facial dysmorphismarrow icon 1 (1.5%) 0 (0.0%) 65 (98.5%)
116 Panhypogammaglobulinemiaarrow icon 1 (1.5%) 0 (0.0%) 65 (98.5%)
117 Asthmaarrow icon 1 (1.5%) 0 (0.0%) 65 (98.5%)
118 Decreased IgM levelsarrow icon 0 (0.0%) 2 (3.0%) 64 (97.0%)

Please mind that full curation of this condition has not been completed yet. It is currently ongoing.

Summary of treatment outcomes

[Considering only Definitive and Possible cases]

Treatment ⓘ Responses & clinical indications
Immunosuppressive agents Moderate (1) for Autoimmune hemolytic anemia
Corticosteroids Moderate (1) for Autoimmune hemolytic anemia
Azithromycin Good (1) for Sinopulmonary infections
Sirolimus Negative/Bad (1) for Autoimmune thrombocytopenia
Rituximab Unspecified (1) for Autoimmune thrombocytopenia
Intravenous immunoglobulin therapy Unspecified (8) for Recurrent lower respiratory tract infections; Sinopulmonary infections; unspecified. Moderate (2) for Recurrent lower respiratory tract infections; Sinopulmonary infections. Good (2) for (unusual) Respiratory tract infection; Sinopulmonary infections. Negative/Bad (1) for Sinopulmonary infections
Antibiotics Good (1) for Sinopulmonary infections. Unspecified (1) for unspecified
Subcutaneous Immunoglobulin infusions Good (2) for Recurrent lower respiratory tract infections; Sinopulmonary infections. Unspecified (2) for Sinopulmonary infections; unspecified
splenectomy Good (1) for Autoimmune thrombocytopenia. Unspecified (1) for Autoimmune hemolytic anemia
Anti-neoplastic agents Negative/Bad (1) for Autoimmune thrombocytopenia. Unspecified (1) for Autoimmune thrombocytopenia
Surgery Good (1) for Autoimmune thrombocytopenia. Unspecified (1) for Autoimmune hemolytic anemia
Hematopoietic stem cell transplantation Negative/Bad (1) for unspecified. Unspecified (1) for unspecified
Chemotherapy Excelent/Remision (2) for Diffuse large B-cell lymphoma; Hodgkin lymphoma

Please mind that full curation of this condition has not been completed yet. It is currently ongoing.