Table 1 Expected disease, molecular diagnosis, and potential treatment options for PID patients with diagnoses
Solved European cases | |||||||||
|---|---|---|---|---|---|---|---|---|---|
Patient ID | Referred from | Gender | Age | Clinical diagnosis/expected disease | Mutation inheritance | ACMG variant class | Mutation(s) identified | Treatment options | Ref treatment |
134.1 | Finland | Female | 4 | ADA2 deficiency | AR (hom) | 5/5 | CECR1 p.(R169Q/R169Q) | Anti-TNF treatment | [40] |
1.1 | Netherlands | Female | 50 | APECED | AR (hom) | 5/5 | AIRE p.(R257*/R257*) | Â | Â |
217.1 | Netherlands | Female | 23 | Chronic granulomatous disease | AR (hom) | 5/5 | NCF2 p.(Y293*/Y293*) | * Specific prophylaxis bacterial and fungal (IFN-γ treatment) consider HSCT | |
70.1 | Netherlands | Female | 27 | Ciliary diskinesia | AR (hom) | 4/4 | RSPH9 p.(M1T/M1T) | Possibility for lung transplantation due to diagnosis of PCD. | [34] |
46.1 | Finland | Female | 15 | Chronic mucocutaneous candidiasis | AD | 4 | STAT1 p.(Q243E/wt) | Ruxolitinib; consider HSCT; IgG replacement therapy | |
149.1 | Netherlands | Female | 55 | Chronic mucocutaneous candidiasis | AD | 5 | STAT1 p.(Q271P/wt) | Ruxolitinib; consider HSCT; IgG replacement therapy | |
222.1 | Netherlands | Male | 29 | Complement deficiency | AR (hom) | 5/5 | C7 p.(G379R/G379R) | * Prophylaxis: vaccination against meningococcus | [46] |
103.1 | Netherlands | Male | 48 | CVID | AD | 5 | NFKB1 p.(S302fs/wt) | IgG replacement therapy | Â |
116.1 | Netherlands | Male | 52 | CVID | AR (hom) | 5/5 | CECR1 p.(L503fs/L503fs) | Anti-TNF treatment | [40] |
169.1 | Netherlands | Male | 57 | CVID, malignancies | XL | 4 | MAGT1 p.(S24*) | IgG replacement therapy Mg supplement therapy: Clinical trial NCT02496676 | [49] |
227.1 | Netherlands | Male | 57 | Familial cold autoinflammatory syndrome | AD | 5 | NLRC4 p.(S445P/wt) | Anti-IL-1 treatment | [53] |
32.1 | Netherlands | Female | 11Â months | Hermansky-Pudlak syndrome | AR (CH) | 4/4 | AP3B1 p.(K59fs/D613fs) | Â | Â |
76.1 | Netherlands | Female | 29 | HSV infections | AD | 5 | GATA2 p.(R86fs /wt) | HSCT | [35] |
142.1 | Netherlands | Female | 20 | Hyper IgE syndrome | AD | 5 | CFTR p.(W1282*/wt) | Â | Â |
162.1 | Netherlands | Male | 9 | IgG deficiency | AD | 5 | TNFRSF13B p.(C104R/wt) | Â | Â |
213.1 | Netherlands | Male | 3Â months | Interstitial lung disease | AR (hom) | 4/4 | DHFR p.(G21R/G21R) | Folinic acid treatment | [51] |
213.2 | Netherlands | Female | 1 | Unknown (affected sibling 213.1) | AR (hom) | 4/4 | DHFR p.(G21R/G21R) | Folinic acid treatment | [51] |
33.1 | Netherlands | Male | 53 | Joint, skin, upper respiratory tract infections | AD | 4 | CXCR4 p.(S343fs/wt) | Plerixafor; CXCR4 antagonist future treatment option | [29] |
69.1 | Netherlands | Male | 9 | Kabuki syndrome | AD | 5 | KMT2D p.(E5425K/wt) | Â | Â |
29.1 | Netherlands | Female | 28 | PAPA syndrome | AD | 5 | PSTPIP1 p.(E250K/wt) | Anti-IL-1 treatment | [28] |
220.1 | Netherlands | Female | 16 | Recurrent infections, IFN-γ deficiency | AD | 4 | CARD11 p.(T43P/wt) | Glutamine supplementation (IFN-γ treatment) | [50] |
AD | 4 | MEFV p.(M680I/wt) | Colchicine anti-IL-1 treatment | [52] | |||||
173.1 | Netherlands | Female | 12 | Recurrent urticaria | AD | 5 | NLRP1 p.(L332fs/wt) | Anti-IL-1 treatment | Â |
52.1 | Netherlands | Male | 4 | Shwachman-Diamond | AD | 5 | TERC n.(37A>G/wt) | Â | Â |
159.1 | Finland | Male | 1 | X-linked thrombocytopenia | XL | 5 | WAS p.(V75M) | HSCT | [39] |
Solved Saudi Arabian cases | |||||||||
202.1 | Saudi Arabia | Female | 7 | Autoimmune lymphoproliferative syndrome | AD | 5 | CARD11 p.(G123S/wt) | Glutamine supplementation; IFN-γ treatment | [50] |
147.1 | Saudi Arabia | Female | 6 | Autoimmune lymphoproliferative syndrome, anti-HCV | AR (hom) | 4/4 | CASP8 p.(A155S/A155S) | Â | Â |
AD | 5 | CBL c.(1228-2A>G/wt) | Â | Â | |||||
83.1 | Saudi Arabia | Male | 2 | Bare lymphocyte syndrome II | AR (hom) | 5/5 | RFXANK p.(D121V/D121V) | HSCT | [37] |
AD | 5 | INSR p(R145C/wt) | Â | Â | |||||
106.1 | Saudi Arabia | Male | 5Â months | Bare lymphocyte syndrome II | AR (hom) | 5/5 | RAG1 p.(K186fs/K186fs) | HSCT | [8] |
185.1 | Saudi Arabia | Female | 8Â months | Bare lymphocyte syndrome II | AR (hom) | 5/5 | RFX5 p.(V378fs/V378fs) | HSCT | [37] |
148.1 | Saudi Arabia | Male | 6 | Complement deficiency | AR (hom) | 5/5 | C8A p.(Y210*/Y210*) | * Prophylaxis: vaccination against meningococcal disease | [46] |
129.1 | Saudi Arabia | Female | 8 months | Chronic granulomatous disease | AR (hom) | 5/5 | CYBA c.(58+4-7del/58+4-7del) | * Specific prophylaxis bacterial and fungal (IFN-γ treatment); consider HSCT | |
161.1 | Saudi Arabia | Male | 2 | Chronic granulomatous disease | AR (hom) | 5/4 | CYBA p.(A117E/A117E) | * Specific prophylaxis bacterial and fungal (IFN-γ treatment); consider HSCT | |
165.1 | Saudi Arabia | Female | 8 | Chronic granulomatous disease | AR (hom) | 5/5 | CEBPE p.(R135*/R135*) | Consider anti-inflammatory therapy | Â |
168.1 | Saudi Arabia | Male | 3 | Chronic granulomatous disease | XL | 5 | CYBB p.(E347fs) | * Specific prophylaxis bacterial and fungal (IFN-γ treatment); consider HSCT | |
156.1 | Saudi Arabia | Female | 3 | Congenital neutropenia, myelofibrosis | AR (hom) | 4/4 | VPS45 p.(L410P/L410P) | HSCT | [47] |
113.1 | Saudi Arabia | Female | 13 | Dyskeratosis congenita | AR (hom) | 4/4 | WRAP53 p.(R387C/R387C) | Â | Â |
122.1 | Saudi Arabia | Female | 19 | Gray platelet syndrome | AR (hom) | 5/5 | ITGA2B p.(R1026W/R1026W) | Â | Â |
126.1 | Saudi Arabia | Female | 11 | Hypogammaglobulinemia | AR (hom) | 5/5 | DNMT3B p.(V836M/V836M) | Consider HSCT; IgG replacement therapy | [41] |
127.1 | Saudi Arabia | Female | 10 | Hypogammaglobulinemia, bronchiectasis | AR (hom) | 5/5 | ZBTB24 p.(Q498fs/Q498fs) | Consider HSCT; IgG replacement therapy | [42] |
127.2 | Saudi Arabia | Female | 12 | Hypogammaglobulinemia | AR (hom) | 5/5 | ZBTB24 p.(Q498fs/Q498fs) | Consider HSCT; IgG replacement therapy | [42] |
138.1 | Saudi Arabia | Male | 1 | Hypogammaglobulinemia | AR (hom) | 5/5 | AK2 p.(A182D/A182D) | Consider HSCT; IgG replacement therapy | [45] |
138.2 | Saudi Arabia | Female | 4 | Hypogammaglobulinemia | AR (hom) | 5/5 | AK2 p.(A182D/A182D) | Consider HSCT; IgG replacement therapy | [45] |
189.1 | Saudi Arabia | Female | 4 | Hypogammaglobulinemia | AR (hom) | 5/5 | DNMT3B p.(V836M/V836M) | Consider HSCT; IgG replacement therapy | [41] |
189.2 | Saudi Arabia | Male | 1 | Hypogammaglobulinemia | AR (hom) | 5/5 | DNMT3B p.(V836M/V836M) | Consider HSCT; IgG replacement therapy | [41] |
196.1 | Saudi Arabia | Male | 7 | Hypogammaglobulinemia | AR (hom) | 5/5 | DNMT3B p.(V836M/V836M) | Consider HSCT; IgG replacement therapy | [41] |
198.1 | Saudi Arabia | Male | 2 | Hypogammaglobulinemia | AR (hom) | 5/5 | JAK3 p.(R403H/R403H) | HSCT | [8] |
204.1 | Saudi Arabia | Male | 6Â months | Hypogammaglobulinemia | AR (hom) | 5/5 | DNMT3B p.(V836M/V836M) | Consider HSCT; IgG replacement therapy | [41] |
100.1 | Saudi Arabia | Female | 8 | IgG deficiency | AD | 5 | PIK3R1 c.(1425+1G>T/ wt) | IgG replacement therapy | [38] |
186.1 | Saudi Arabia | Male | 6 | Microcytic anemia | AD | 4 | HBB p.(Q7V/wt) | Â | Â |
236.1 | Saudi Arabia | Male | 6 | Non-immune hemolytic anemia | XL | 5 | G6PD p.(V461G) | * Dietary: Avoidance of fava beans and specific drugs | [54] |
240.1 | Saudi Arabia | Female | 2Â months | Pancytopenia | AR (hom) | 5/5 | MTHFD1 p.(R173C/R173C) | Folic acid and folinic acid treatment | [51] |
94.1 | Saudi Arabia | Female | 8 | Pancytopenia, hyper- and hypogammaglobulinemia | AR (CH) | 5/3 | FANCA p.(L910fs/C1142Y) | Â | Â |
114.1 | Saudi Arabia | Female | 8Â months | SCID | AR (hom) | 4/4 | DCLRE1C p.(P117Q/P117Q) | Consider HSCT | [8] |
115.1 | Saudi Arabia | Female | 8Â months | SCID | AR (hom) | 4/4 | ZAP70 p.(S524C/S524C) | HSCT | [8] |
105.1 | Saudi Arabia | Male | 5Â months | SCID, HLH | XL | 5 | IL2RG p.(I273fs) | Consider HSCT, IgG replacement therapy | [8] |
112.1 | Saudi Arabia | Male | 8Â months | SCID, Omenn syndrome | AR (hom) | 5/5 | RAG1 p.(K186fs/K186fs) | HSCT | [8] |
146.1 | Saudi Arabia | Male | 11Â months | SCID, HLH | AR (hom) | 5/5 | JAK3 Ex10 Deletion | HSCT | [8] |
154.1 | Saudi Arabia | Male | 3Â months | SCID, BCGitis | AR (hom) | 4/4 | RAG2 p.(K106E/K106E) | HSCT | [8] |
199.1 | Saudi Arabia | Male | 3 | SCID, Burkitt’s lymphoma | AR (hom) | 4/4 | LCK p.(R480fs/R480fs) | HSCT | [8] |
84.1 | Saudi Arabia | Male | 9 | Severe eczema | AD | 4 | SAMHD1 p.(F329fs/wt) | Consider anti-IL-5 or anti-IL4R treatment | Â |
61.1 | Saudi Arabia | Female | 12 | Severe infections, pancytopenia | AD | 4 | CTLA4 p.(G146R /wt) | Abatacept (recombinant CTLA4) | [33] |
82.1 | Saudi Arabia | Female | 4 | Severe infections, thrombocytopenia | AR (hom) | 5/5 | LRBA p.(T1587fs/T1587fs) | Abatacept (recombinant CTLA4) | [36] |
190.1 | Saudi Arabia | Male | 4 | Severe lung infections | AR (hom) | 5/5 | AK2 p.(A182D/A182D) | Consider HSCT; IgG replacement therapy | [45] |
145.1 | Saudi Arabia | Female | 5Â months | Severe infections, hypergammaglobulinemia | AR (hom) | 5/5 | CFTR c.(579+1G>A/579+1G>A) | Â | Â |
239.1 | Saudi Arabia | Female | 4Â months | Severe infections, hemolytic anemia | AD | 4 | ANK1 p.(Q1313*/wt) | Â | Â |
242.1 | Saudi Arabia | Female | 4 | Severe infections, leukocytosis, hypergammaglobulinemia | AD | 5 | STAT3 p.(V713M/wt) | * Specific prophylaxis bacterial and fungal (IFN-γ treatment) | [32] |
160.1 | Saudi Arabia | Female | 2 | Shwachman-Diamond, CD3 deficiency | AR (hom) | 4/4 | PRF1 p.(R410P/R410P) | Possible T cell gene therapy (under development) | [48] |
153.1 | Saudi Arabia | Male | 15 | T cell acute lymphoblastic leukemia | AR (hom) | 5/5 | NBN p.(Y197fs/Y197fs) | Â | Â |
AD | 4 | RPL5 p.(G140S/wt) | Â | Â | |||||
107.1 | Saudi Arabia | Male | 21 | Thrombocytopenia | XL | 5 | WAS p.(T48A) | HSCT | [39] |
188.1 | Saudi Arabia | Male | 6 months | TORCH | AR (hom) | 4/4‡ | RNASEH2B p.(D119G/D119G) |  |  |
195.1 | Saudi Arabia | Male | 1Â months | Transaldolase deficiency | AR (hom) | 5/5 | TALDO1 p.(Q265fs/Q265fs) | Â | Â |
193.1 | Saudi Arabia | Male | 38 | Viral infections, autoimmune manifestations, thrombocytopenia | AR (hom) | 5/5 | C7 p.(G378R/G378R) | * Prophylaxis: vaccination against meningococcus | [46] |