PKCδ deficiency reported in the literature
| Reference . | Age at onset . | Sex . | Ethnicity . | Genetic variant . | Initial presentation . | Infections . | Lymphoproliferation . | Autoimmunity . | Laboratory . | Treatment(s) . | Age at last follow-up . | Alive/dead . |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Salzer et al., 2013, PT1 (2) | Infancy | M | Turkish | c.1352+1G>A | Recurrent infections | URTI (i.e., pneumonia), LRTI, UTIs, gastroenteritis otitis media, and herpes virus viremia | Hepatosplenomegaly and lymphadenopathy | Nephrotic syndrome, nonspecific reactive follicular hyperplasia, relapsing polychondritis, hypothyroidism, antiphospholipid syndrome, and SLE | Progressive reduction in B cells, reduced memory B cells, increased CD21low B cells, low IgG levels, and elevated IgA and IgM levels | Steroids, rituximab, MMF, IVIG, enalapril, anticoagulants, and thyroid hormone replacement | 12 years | Alive |
| Belot et al., 2013, PTV1, V3, V4 (10) | 10 years | F | White, of Northern European extraction | c.1528G>A | Discoid lupus rash and arthritis | None reported | Hepatomegaly | Alopecia, lupus nephritis, arthritis, chronic cutaneous lupus, WHO type 2 glomerulonephritis with severe nephrotic syndrome, chronic renal failure, SLE, and CNS vasculitis | Lymphopenia (B and T cells), positive ANAs (1:640) and anti-dsDNA antibodies, low C3 and C4, and elevated IgA | Steroids, hydroxychloroquine, Azathioprine, methotrexate, and MMF | 24 years | Alive |
| 3 years | F | White, of Northern European extraction | c.1528G>A | Diffuse lymphoproliferation and AIHA | P. aeruginosa septic shock | Lymphadenopathy, multiple compressive adenopathy with mediastinal involvement and hepatosplenomegaly | SLE, AIHA, serositis, pancreatitis, ITP, lupus rash, and lupus nephritis | Lymphopenia, but increased CD3+ T cells, undetectable double-negative TCRα/β T cells, positive ANAs (1:640) and anti-dsDNA antibodies, and low C3 and C4 | Immunosuppressive treatments | 8 years | Died at age 13 years (end-stage kidney failure complicated by Pseudomonas sustained septic shock) | |
| 6 years | M | White, of Northern European extraction | c.1528G>A | Lupus nephritis | | None | Renal flare with malar rash and arthritis SLE | Increased immature and naive B cells, reduced memory B cells, positive ANAs, and anti-dsDNA antibodies | Steroids (prednisolone) and MMF | 13 years | Alive | |
| Kuehn et al., 2013, PT1 (1) | 3 years | M | Hispanic | c.1840C>T | Recurrent otitis, sinusitis, persistent lymphadenopathy, hepatosplenomegaly, and intermittent fevers | Recurrent otitis media/sinusitis, and persistent EBV | Hepatosplenomegaly and mediastinal lymphadenitis (with superior vena cava syndrome) | SLE and AIHA | CD5+ majority B lymphocytosis; reduced class-switched memory B cells; elevated DNT αβ and DNT γδ; low levels of NK cells and NK cell cytolytic activity; increased ESR, CRP, ALT, and AST; hypergammaglobulinemia; positive ANAs; anti-RNP; anti-Smith; anti-SSA | Steroids (prednisone) and sirolimus | 7 years | Alive |
| Kiykim et al., 2015, PT6 (11) | Infancy | M | Turkish | c.742G>A | Recurrent fever | Pneumonia, gastroenteritis, and CMV | Hepatosplenomegaly and lymphadenopathy | SLE | Naive majority B lymphocytosis and CD21low, reduced levels of switched memory B cells, increased IgM, and reduced NK functionality | Ganciclovir, IVIG, topical steroids, hydroxychloroquine, IVIG, and prophylactic antibiotics | 3.5 years | Alive |
| Lei et al., 2018, PT II-1, PT II-2, and PT 11-3 (12) | 1 year | F | Endogamous Pakistani | c.1294G>T | Constitutional symptoms (intermittent fever, night sweats, fatigue), severe thrombocytopenia, photosensitive and petechial rash, scarring alopecia, and hepatosplenomegaly | NR | Splenomegaly and lymphadenopathy | SLE (acuta cutaneous lupus, oral/nasal ulcers) | AIHA, thrombocytopenia, leukopenia, positive ANA (1:1,280), anti-dsDNA, antiphospholipid antibody, low complement, elevated CRP and ESR, elevated IgG, and low levels of C4 | Steroid, rituximab (discontinued for adverse reaction), IVIG, hydroxychloroquine, Azathioprine, and Ofatumumab | NR | Alive |
| 1 year | F | Endogamous Pakistani | c.1294G>T | Constitutional symptoms (intermittent fever, night sweats, fatigue), severe thrombocytopenia, photosensitive and petechial rash, scarring alopecia, hepatosplenomegaly | NR | Hepatosplenomegaly, lymphadenopathy | SLE (acute cutaneous lupus, serositis, and renal impairment) | AIHA, thrombocytopenia, leukopenia, slight neutropenia, positive ANA (1:1,280), anti-dsDNA, antiphospholipid antibody, and low complement, elevated CRP and ESR, elevated albumin/creatinine ratio, hypergammaglobulinemia, and low levels of C4 | Steroid, IVIG, rituximab (discontinued for adverse reaction),h ydroxychloroquine, Azathioprine, and Ofatumumab | NR | Alive | |
| 26 mo | M | Endogamous Pakistani | c.1294G>T | Constitutional symptoms (intermittent fever, night sweats, fatigue), severe thrombocytopenia, photosensitive and petechial rash, scarring alopecia, and hepatosplenomegaly | NR | Hepatosplenomegaly | SLE (acute cutaneous lupus) | AIHA, thrombocytopenia, positive ANA (1:1,280), anti-dsDNA, anti-Smith antibody, and low complement | Steroid (IV methylprednisolone), IVIG, and rituximab | NR | Alive | |
| Sharifinejad et al., 2020, PT10 (13) | Infancy | M | Afghan | c.1293_1294insA | Recurrent oral candidiasis, nonsevere upper respiratory and gastrointestinal tract infections, and food allergy | Pneumonia, oral candidiasis, and recurrent gastroenteritis | Hepatosplenomegaly and lymphadenopathy | SLE | Increased DNT, reduced NK number, increased IgG, and nonprotective antidiphtheria | Corticosteroids, antibiotic prophylaxis | 13 years | Alive |
| Neehus et al., 2021, PT13-17 (14) | 1 year | F | Turkish | c.571+2dup | BCGosis, fever, left axillary, retroauricular, and cervical lymphadenopathies | BCGosis, Salmonella bacteremia, Staphylococcus aureus lymphadenitis, and recurrent gingivitis | Lymphadenopathy and hepatosplenomegaly | SLE | Elevated naive B cells and reduced B memory, with elevated CD21low and transitional cells, hypogammaglobulinemia, ANA+, and anti-dsDNA+ | Steroids IVIG Antimycobacterial (ceftriaxone); antibiotic prophylaxis (amoxicillin) | 14 years | Alive |
| 7 mo | M | Turkish | c.1384C>T | Fever, diarrhea, hepatosplenomegaly, failure to thrive, left axillary lymphadenopathy with purulent discharge, and BCGitis | BCGitis, recurrent gastroenteritis | Hepatosplenomegaly | AIHA | Impaired DHR test and ANA+ | Steroids Isoniazid Rifampicin | 10 years | Alive | |
| 7 mo | M | Turkish | c.1384C>T | BCGitis | BCGitis, recurrent gastroenteritis and shingles | Lymphadenopathy and hepatosplenomegaly | AIHA | Impaired DHR test and ANA+ | Steroids Isoniazid Rifampicin IVIG | 7 years | Alive | |
| 1 year | F | Irani | c.642del | BCGitis | BCGitis | Hepatosplenomegaly and lymphadenopathy | None | Impaired DHR test and nonprotective antibody responses to tetanus and diphtheria | Isoniazid Rifampicin Azithromycin | 3 years | Alive | |
| NR | M | Irani | c.642del | Asymptomatic | None | None | None | Impaired DHR test | No treatment | 6 years | Alive | |
| Gu et al., 2021, PT16-17 (15) and Jefferson et al., 2023 (3) | 6 y | M | Chinese | c.36T>G | Lymphadenopathy, splenomegaly, and recurrent infections | NR | Splenomegaly and lymphadenopathy | Pancytopenia | Positive antibodies for EBV, CMV, herpes simplex virus, and rubella viruses, increased TCRαβ DNT, increased CD8+ T cells and IgG, and low levels of NK cells | Steroids, IRT, and sirolimus | 10 years | Alive |
| NR | F | Chinese | c.36T>G | Lymphadenopathy, splenomegaly, and anemia | NR | Splenomegaly and lymphadenopathy | Anemia | NR | NR | NR | NR | |
| Yang et al., 2022, PT18 (18) | 5 mo | F | Chinese | c.661C>T | Recurrent fever, respiratory tract infections, and lymphadenopathy | URTIs and BCGosis | Multiple lymphadenopathy (abdominal mesenteric lymph nodes invading the abdominal wall), bone marrow hyperplasia, and hepatosplenomegaly | NR | Increased DNT, elevated CD8+ T cells, low levels of CD4+ T cells, and CRP positive | Isoniazid, rifampicin, ethambutol, sirolimus, IFN-γ, and antibiotics | 8 years | Alive |
| Neehus et al., 2022, PT19 (19) | 2 years | F | American | c.285C>A/c.376C>T | URTI, lymphadenitis | Burkholderia cepacia and Mycobacterium lentiflavum lymphadenopathy | Infectious lymphadenopathy | None | Low levels of CD4+ T cells, decreased relative proportions of CD27+IgD+ and CD27+IgD− memory B cells, and abnormally low DHR test | Cotrimoxazole, isoniazid, and Rifampicin | 5 years | Alive |
| Roderick et al., 2023, PT20-21 (9) | 9 mo | M | British | c.788-2A>G/c.571C>T | Listeria meningitis | Listeria meningitis, Enterococcus faecium bacteremia, varicella and shingles, invasive Candida infection, recurrent episodes of Achromobacter xylosoxidans cervical lymphadenitis, and early-onset enterocolitis | Lymphoid hyperplasia and splenomegaly | SLE, AIHA, and ITP | Increased DNTs, low B cells with low IgG with high IgM, positive anticardiolipin antibodies, Coombs positive, and positive thyroid peroxidase antibodies | Steroids, IVIG, rituximab, Sirolimus, Hydroxychloroquine, HSCT, and cyclosporine (for GVHD prophylaxis) | NR | Alive |
| 20 mo | F | British | c.788-2A>G/c.571C>T | Sepsis due to nontypeable Haemophilus influenzae | Early-onset enterocolitis | Lymphoid hyperplasia, splenomegaly | SLE | Increased DNTs, low B cells with low IgG and high IgM, positive anticardiolipin antibodies, and GAD antibody-positive | IVIG replacement therapy, rituximab, sirolimus (stopped because of oral ulceration), MMF, and hydroxychloroquine HSCT | 8.5 years | Alive |
| Reference . | Age at onset . | Sex . | Ethnicity . | Genetic variant . | Initial presentation . | Infections . | Lymphoproliferation . | Autoimmunity . | Laboratory . | Treatment(s) . | Age at last follow-up . | Alive/dead . |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Salzer et al., 2013, PT1 (2) | Infancy | M | Turkish | c.1352+1G>A | Recurrent infections | URTI (i.e., pneumonia), LRTI, UTIs, gastroenteritis otitis media, and herpes virus viremia | Hepatosplenomegaly and lymphadenopathy | Nephrotic syndrome, nonspecific reactive follicular hyperplasia, relapsing polychondritis, hypothyroidism, antiphospholipid syndrome, and SLE | Progressive reduction in B cells, reduced memory B cells, increased CD21low B cells, low IgG levels, and elevated IgA and IgM levels | Steroids, rituximab, MMF, IVIG, enalapril, anticoagulants, and thyroid hormone replacement | 12 years | Alive |
| Belot et al., 2013, PTV1, V3, V4 (10) | 10 years | F | White, of Northern European extraction | c.1528G>A | Discoid lupus rash and arthritis | None reported | Hepatomegaly | Alopecia, lupus nephritis, arthritis, chronic cutaneous lupus, WHO type 2 glomerulonephritis with severe nephrotic syndrome, chronic renal failure, SLE, and CNS vasculitis | Lymphopenia (B and T cells), positive ANAs (1:640) and anti-dsDNA antibodies, low C3 and C4, and elevated IgA | Steroids, hydroxychloroquine, Azathioprine, methotrexate, and MMF | 24 years | Alive |
| 3 years | F | White, of Northern European extraction | c.1528G>A | Diffuse lymphoproliferation and AIHA | P. aeruginosa septic shock | Lymphadenopathy, multiple compressive adenopathy with mediastinal involvement and hepatosplenomegaly | SLE, AIHA, serositis, pancreatitis, ITP, lupus rash, and lupus nephritis | Lymphopenia, but increased CD3+ T cells, undetectable double-negative TCRα/β T cells, positive ANAs (1:640) and anti-dsDNA antibodies, and low C3 and C4 | Immunosuppressive treatments | 8 years | Died at age 13 years (end-stage kidney failure complicated by Pseudomonas sustained septic shock) | |
| 6 years | M | White, of Northern European extraction | c.1528G>A | Lupus nephritis | | None | Renal flare with malar rash and arthritis SLE | Increased immature and naive B cells, reduced memory B cells, positive ANAs, and anti-dsDNA antibodies | Steroids (prednisolone) and MMF | 13 years | Alive | |
| Kuehn et al., 2013, PT1 (1) | 3 years | M | Hispanic | c.1840C>T | Recurrent otitis, sinusitis, persistent lymphadenopathy, hepatosplenomegaly, and intermittent fevers | Recurrent otitis media/sinusitis, and persistent EBV | Hepatosplenomegaly and mediastinal lymphadenitis (with superior vena cava syndrome) | SLE and AIHA | CD5+ majority B lymphocytosis; reduced class-switched memory B cells; elevated DNT αβ and DNT γδ; low levels of NK cells and NK cell cytolytic activity; increased ESR, CRP, ALT, and AST; hypergammaglobulinemia; positive ANAs; anti-RNP; anti-Smith; anti-SSA | Steroids (prednisone) and sirolimus | 7 years | Alive |
| Kiykim et al., 2015, PT6 (11) | Infancy | M | Turkish | c.742G>A | Recurrent fever | Pneumonia, gastroenteritis, and CMV | Hepatosplenomegaly and lymphadenopathy | SLE | Naive majority B lymphocytosis and CD21low, reduced levels of switched memory B cells, increased IgM, and reduced NK functionality | Ganciclovir, IVIG, topical steroids, hydroxychloroquine, IVIG, and prophylactic antibiotics | 3.5 years | Alive |
| Lei et al., 2018, PT II-1, PT II-2, and PT 11-3 (12) | 1 year | F | Endogamous Pakistani | c.1294G>T | Constitutional symptoms (intermittent fever, night sweats, fatigue), severe thrombocytopenia, photosensitive and petechial rash, scarring alopecia, and hepatosplenomegaly | NR | Splenomegaly and lymphadenopathy | SLE (acuta cutaneous lupus, oral/nasal ulcers) | AIHA, thrombocytopenia, leukopenia, positive ANA (1:1,280), anti-dsDNA, antiphospholipid antibody, low complement, elevated CRP and ESR, elevated IgG, and low levels of C4 | Steroid, rituximab (discontinued for adverse reaction), IVIG, hydroxychloroquine, Azathioprine, and Ofatumumab | NR | Alive |
| 1 year | F | Endogamous Pakistani | c.1294G>T | Constitutional symptoms (intermittent fever, night sweats, fatigue), severe thrombocytopenia, photosensitive and petechial rash, scarring alopecia, hepatosplenomegaly | NR | Hepatosplenomegaly, lymphadenopathy | SLE (acute cutaneous lupus, serositis, and renal impairment) | AIHA, thrombocytopenia, leukopenia, slight neutropenia, positive ANA (1:1,280), anti-dsDNA, antiphospholipid antibody, and low complement, elevated CRP and ESR, elevated albumin/creatinine ratio, hypergammaglobulinemia, and low levels of C4 | Steroid, IVIG, rituximab (discontinued for adverse reaction),h ydroxychloroquine, Azathioprine, and Ofatumumab | NR | Alive | |
| 26 mo | M | Endogamous Pakistani | c.1294G>T | Constitutional symptoms (intermittent fever, night sweats, fatigue), severe thrombocytopenia, photosensitive and petechial rash, scarring alopecia, and hepatosplenomegaly | NR | Hepatosplenomegaly | SLE (acute cutaneous lupus) | AIHA, thrombocytopenia, positive ANA (1:1,280), anti-dsDNA, anti-Smith antibody, and low complement | Steroid (IV methylprednisolone), IVIG, and rituximab | NR | Alive | |
| Sharifinejad et al., 2020, PT10 (13) | Infancy | M | Afghan | c.1293_1294insA | Recurrent oral candidiasis, nonsevere upper respiratory and gastrointestinal tract infections, and food allergy | Pneumonia, oral candidiasis, and recurrent gastroenteritis | Hepatosplenomegaly and lymphadenopathy | SLE | Increased DNT, reduced NK number, increased IgG, and nonprotective antidiphtheria | Corticosteroids, antibiotic prophylaxis | 13 years | Alive |
| Neehus et al., 2021, PT13-17 (14) | 1 year | F | Turkish | c.571+2dup | BCGosis, fever, left axillary, retroauricular, and cervical lymphadenopathies | BCGosis, Salmonella bacteremia, Staphylococcus aureus lymphadenitis, and recurrent gingivitis | Lymphadenopathy and hepatosplenomegaly | SLE | Elevated naive B cells and reduced B memory, with elevated CD21low and transitional cells, hypogammaglobulinemia, ANA+, and anti-dsDNA+ | Steroids IVIG Antimycobacterial (ceftriaxone); antibiotic prophylaxis (amoxicillin) | 14 years | Alive |
| 7 mo | M | Turkish | c.1384C>T | Fever, diarrhea, hepatosplenomegaly, failure to thrive, left axillary lymphadenopathy with purulent discharge, and BCGitis | BCGitis, recurrent gastroenteritis | Hepatosplenomegaly | AIHA | Impaired DHR test and ANA+ | Steroids Isoniazid Rifampicin | 10 years | Alive | |
| 7 mo | M | Turkish | c.1384C>T | BCGitis | BCGitis, recurrent gastroenteritis and shingles | Lymphadenopathy and hepatosplenomegaly | AIHA | Impaired DHR test and ANA+ | Steroids Isoniazid Rifampicin IVIG | 7 years | Alive | |
| 1 year | F | Irani | c.642del | BCGitis | BCGitis | Hepatosplenomegaly and lymphadenopathy | None | Impaired DHR test and nonprotective antibody responses to tetanus and diphtheria | Isoniazid Rifampicin Azithromycin | 3 years | Alive | |
| NR | M | Irani | c.642del | Asymptomatic | None | None | None | Impaired DHR test | No treatment | 6 years | Alive | |
| Gu et al., 2021, PT16-17 (15) and Jefferson et al., 2023 (3) | 6 y | M | Chinese | c.36T>G | Lymphadenopathy, splenomegaly, and recurrent infections | NR | Splenomegaly and lymphadenopathy | Pancytopenia | Positive antibodies for EBV, CMV, herpes simplex virus, and rubella viruses, increased TCRαβ DNT, increased CD8+ T cells and IgG, and low levels of NK cells | Steroids, IRT, and sirolimus | 10 years | Alive |
| NR | F | Chinese | c.36T>G | Lymphadenopathy, splenomegaly, and anemia | NR | Splenomegaly and lymphadenopathy | Anemia | NR | NR | NR | NR | |
| Yang et al., 2022, PT18 (18) | 5 mo | F | Chinese | c.661C>T | Recurrent fever, respiratory tract infections, and lymphadenopathy | URTIs and BCGosis | Multiple lymphadenopathy (abdominal mesenteric lymph nodes invading the abdominal wall), bone marrow hyperplasia, and hepatosplenomegaly | NR | Increased DNT, elevated CD8+ T cells, low levels of CD4+ T cells, and CRP positive | Isoniazid, rifampicin, ethambutol, sirolimus, IFN-γ, and antibiotics | 8 years | Alive |
| Neehus et al., 2022, PT19 (19) | 2 years | F | American | c.285C>A/c.376C>T | URTI, lymphadenitis | Burkholderia cepacia and Mycobacterium lentiflavum lymphadenopathy | Infectious lymphadenopathy | None | Low levels of CD4+ T cells, decreased relative proportions of CD27+IgD+ and CD27+IgD− memory B cells, and abnormally low DHR test | Cotrimoxazole, isoniazid, and Rifampicin | 5 years | Alive |
| Roderick et al., 2023, PT20-21 (9) | 9 mo | M | British | c.788-2A>G/c.571C>T | Listeria meningitis | Listeria meningitis, Enterococcus faecium bacteremia, varicella and shingles, invasive Candida infection, recurrent episodes of Achromobacter xylosoxidans cervical lymphadenitis, and early-onset enterocolitis | Lymphoid hyperplasia and splenomegaly | SLE, AIHA, and ITP | Increased DNTs, low B cells with low IgG with high IgM, positive anticardiolipin antibodies, Coombs positive, and positive thyroid peroxidase antibodies | Steroids, IVIG, rituximab, Sirolimus, Hydroxychloroquine, HSCT, and cyclosporine (for GVHD prophylaxis) | NR | Alive |
| 20 mo | F | British | c.788-2A>G/c.571C>T | Sepsis due to nontypeable Haemophilus influenzae | Early-onset enterocolitis | Lymphoid hyperplasia, splenomegaly | SLE | Increased DNTs, low B cells with low IgG and high IgM, positive anticardiolipin antibodies, and GAD antibody-positive | IVIG replacement therapy, rituximab, sirolimus (stopped because of oral ulceration), MMF, and hydroxychloroquine HSCT | 8.5 years | Alive |
AIHA, autoimmune hemolytic anemia; ALT, alanine aminotransferase; ANA, antinuclear antibody; AST, aspartate aminotransferase; BCG, Bacillus Calmette-Guérin; CMV, cytomegalovirus; CNS, central nervous system; CRP, C-reactive protein; C3; complement component 3; C4; complement component 4; DHR, dihydrorhodamine; DNTs, double-negative T cells; dsDNA, double-stranded DNA; EBV, Epstein-Barr virus; ESR, erythrocyte sedimentation rate; F, female; GAD, glutamic acid decarboxylase; GVHD, graft-versus-host disease; IFN-γ, interferon γ; IRT, immunoglobulin replacement therapy; ITP, immune thrombocytopenia; IVIG, intravenous immunoglobulin; LRTI, lower respiratory tract infection; M, male; MMF, mycophenolate mofetil; NK, natural killer; NR, not reported; PT, patient; RNP, ribonucleoprotein; SLE, systemic lupus erythematous; SSA, Sjögren syndrome type A; TCR, T cell receptor; URTI, upper respiratory tract infections; UTI, urinary tract infection; WHO, World Health Organization.