The Swiss National Registry for Primary Immunodeficiencies: report on the first 6 years' activity from 2008 to 2014

The Swiss National Registry for Primary Immunodeficiency Disorders (PID) was established in 2008, constituting a nationwide network of paediatric and adult departments involved in the care of patients with PID at university medical centres, affiliated teaching hospitals and medical institutions. The registry collects anonymized clinical and genetic information on PID patients and is set up within the framework of the European database for PID, run by the European Society of Immunodeficiency Diseases. To date, a total of 348 patients are registered in Switzerland, indicating an estimated minimal prevalence of 4·2 patients per 100 000 inhabitants. Distribution of different PID categories, age and gender are similar to the European cohort of currently 19 091 registered patients: 'predominantly antibody disorders' are the most common diseases observed (n = 217/348, 62%), followed by 'phagocytic disorders' (n = 31/348, 9%). As expected, 'predominantly antibody disorders' are more prevalent in adults than in children (78 versus 31%). Within this category, 'common variable immunodeficiency disorder' (CVID) is the most prevalent PID (n = 98/217, 45%), followed by 'other hypogammaglobulinaemias' (i.e. a group of non-classified hypogammaglobulinaemias) (n = 54/217, 25%). Among 'phagocytic disorders', 'chronic granulomatous disease' is the most prevalent PID (n = 27/31, 87%). The diagnostic delay between onset of symptoms and diagnosis is high, with a median of 6 years for CVID and more than 3 years for 'other hypogammaglobulinaemias'

Initial presenting manifestations in 16,486 patients with inborn errors of immunity include infections and noninfectious manifestations

none313siBackground: Inborn errors of immunity (IEI) are rare diseases, which makes diagnosis a challenge. A better description of the initial presenting manifestations should improve awareness and avoid diagnostic delay. Although increased infection susceptibility is a well-known initial IEI manifestation, less is known about the frequency of other presenting manifestations. Objective: We sought to analyze age-related initial presenting manifestations of IEI including different IEI disease cohorts. Methods: We analyzed data on 16,486 patients of the European Society for Immunodeficiencies Registry. Patients with autoinflammatory diseases were excluded because of the limited number registered. Results: Overall, 68% of patients initially presented with infections only, 9% with immune dysregulation only, and 9% with a combination of both. Syndromic features were the presenting feature in 12%, 4% had laboratory abnormalities only, 1.5% were diagnosed because of family history only, and 0.8% presented with malignancy. Two-third of patients with IEI presented before the age of 6 years, but a quarter of patients developed initial symptoms only as adults. Immune dysregulation was most frequently recognized as an initial IEI manifestation between age 6 and 25 years, with male predominance until age 10 years, shifting to female predominance after age 40 years. Infections were most prevalent as a first manifestation in patients presenting after age 30 years. Conclusions: An exclusive focus on infection-centered warning signs would have missed around 25% of patients with IEI who initially present with other manifestations.noneThalhammer J.; Kindle G.; Nieters A.; Rusch S.; Seppanen M.R.J.; Fischer A.; Grimbacher B.; Edgar D.; Buckland M.; Mahlaoui N.; Ehl S.; Boztug K.; Brunner J.; Demel U.F.; Forster-Waldl E.; Gasteiger L.M.; Goschl L.; Kojic M.; Schroll A.; Seidel M.G.; Wintergerst U.; Wisgrill L.; Sharapova S.O.; Goffard J.-C.; Kerre T.; Meyts I.; Roosens F.; Smet J.; Haerynck F.; Eric Z.P.; Milenova V.; Gagro A.; Richter D.; Chovancova Z.; Hlavackova E.; Litzman J.; Milota T.; Sediva A.; Elaziz D.A.; Alkady R.S.; El Sayed El Hawary R.; Eldash A.S.; Galal N.; Lotfy S.; Meshaal S.S.; Reda S.M.; Sobh A.; Elmarsafy A.; Brosselin P.; Courteille V.; De Vergnes N.; Kracker S.; Pergent M.; Randrianomenjanahary P.; Ahrenstorf G.; Albert M.H.; Ankermann T.; Atschekzei F.; Baumann U.; Becker B.C.; Behrends U.; Belohradsky B.H.; Biegner A.-K.; Binder N.; Bode S.F.N.; Boesecke C.; Boetticher B.; Borte M.; Borte S.; Classen C.F.; Dirks J.; Duckers G.; El-Helou S.; Ernst D.; Fasshauer M.; Fecker G.; Felgentreff K.; Foell D.; Ghosh S.; Girschick H.J.; Goldacker S.; Graf N.; Graf D.; Greil J.; Hanitsch L.G.; Hauck F.; Heeg M.; Heine S.I.; Henes J.C.; Hoenig M.; Holzer U.; Holzinger D.; Horneff G.; Hundsdoerfer P.; Jablonka A.; Jakoby D.; Joean O.; Kaiser-Labusch P.; Klemann C.; Kobbe R.; Korholz J.; Kramm C.M.; Kruger R.; Landwehr-Kenzel S.; Lehmberg K.; Liese J.G.; Lippert C.F.; Maccari M.E.; Masjosthusmann K.; Meinhardt A.; Metzler M.; Morbach H.; Muller I.; Naumann-Bartsch N.; Neubert J.; Niehues T.; Peter H.-H.; Rieber N.; Ritterbusch H.; Rockstroh J.K.; Roesler J.; Schauer U.; Scheible R.; Schmalzing M.; Schmidt R.E.; Schneider D.T.; Schreiber S.; Schuetz C.; Schulz A.; Schulze-Koops H.; Schulze-Sturm U.; Schuster V.; Schwaneck E.C.; Schwarz K.; Schwarze-Zander C.; Sirin M.; Skapenko A.; Sogkas G.; Sparber-Sauer M.; Speckmann C.; Steinmann S.; Stiehler S.; Tenbrock K.; von Bernuth H.; Warnatz K.; Wasmuth J.-C.; Weiss M.; Witte T.; Wittke K.; Wittkowski H.; Zeuner R.A.; Farmaki E.; Hatzistilianou M.N.; Kakkas I.; Kanariou M.G.; Kapousouzi A.; Liatsis E.; Maggina P.; Papadopoulou-Alataki E.; Raptaki M.; Speletas M.; Tantou S.; Goda V.; Krivan G.; Marodi L.; Abolhassani H.; Aghamohammadi A.; Rezaei N.; Feighery C.; Leahy T.R.; Ryan P.; Batzir N.A.; Garty B.Z.; Tamary H.; Aiuti A.; Amodio D.; Azzari C.; Barzaghi F.; Baselli L.A.; Cancrini C.; Carrabba M.; Cazzaniga M.; Cesaro S.; Chinello M.; Danieli M.G.; Dellepiane R.M.; Fabio G.; Gambineri E.; Lodi L.; Lougaris V.; Marasco C.; Martire B.; Marzollo A.; Milito C.; Moschese V.; Pignata C.; Plebani A.; Porta F.; Quinti I.; Ricci S.; Soresina A.; Tommasini A.; Vacca A.; Vanessa C.; Blaziene A.; Sitkauskiene B.; Gowin E.; Heropolitanska-Pliszka E.; Pietrucha B.; Szaflarska A.; Wiesik-Szewczyk E.; Wolska-Kusnierz B.; Esteves I.; Faria E.; Marques L.H.; Neves J.F.; Silva S.L.; Teixeira C.; Pereira da Silva S.; Capilna B.R.; Guseva M.N.; Shcherbina A.; Bobcakova A.; Ciznar P.; Gabzdilova J.; Jesenak M.; Kapustova L.; Orosova J.; Petrovicova O.; Raffac S.; Kopac P.; Allende L.M.; Antoli A.; Blanch G.R.; Carbone J.; Dieli-Crimi R.; Garcia-Prat M.; Gil-Herrera J.; Gonzalez-Granado L.I.; Agullo P.L.; Olbrich P.; Parra-Martinez A.; Paz-Artal E.; Pleguezuelo D.E.; Rodriguez N.S.; Sanchez-Ramon S.; Santos-Perez J.L.; Solanich X.; Soler-Palacin P.; Gonzalez-Amores M.; Ekwall O.; Fasth A.; Bitzenhofer-Gruber M.; Candotti F.; Dimitriou F.; Heininger U.; Holbro A.; Jandus P.; Kolios A.G.A.; Marschall K.; Schmid J.P.; Posfay-Barbe K.M.; Prader S.; Reichenbach J.; Steiner U.C.; Truck J.; Bredius R.G.; de Kruijf- Bazen S.; de Vries E.; Henriet S.S.V.; Kuijpers T.W.; Potjewijd J.; Rutgers A.; Stol K.; van Aerde K.J.; Van den Berg J.M.; van de Ven A.A.J.M.; Montfrans J.; Aydemir S.; Baris S.; Dogu F.; Ikinciogullari A.; Karakoc-Aydiner E.; Kilic S.S.; Kiykim A.; Kokcu Karadag S.I.; Kutukculer N.; Ocak S.; UNAL E.; Boyarchuk O.; Hilfanova A.; Kostyuchenko L.V.; Alachkar H.; Arkwright P.D.; Baxendale H.E.; Bernatoniene J.; Coulter T.I.; Garcez T.; Goddard S.; Gompels M.M.; Grigoriadou S.; Herriot R.; Herwadkar A.; Huissoon A.; Ibberson L.; Nademi Z.; Noorani S.; Parvin S.; Steele C.L.; Thomas M.; Waruiru C.; Yong P.F.K.; Bourne H.Thalhammer, J.; Kindle, G.; Nieters, A.; Rusch, S.; Seppanen, M. R. J.; Fischer, A.; Grimbacher, B.; Edgar, D.; Buckland, M.; Mahlaoui, N.; Ehl, S.; Boztug, K.; Brunner, J.; Demel, U. F.; Forster-Waldl, E.; Gasteiger, L. M.; Goschl, L.; Kojic, M.; Schroll, A.; Seidel, M. G.; Wintergerst, U.; Wisgrill, L.; Sharapova, S. O.; Goffard, J. -C.; Kerre, T.; Meyts, I.; Roosens, F.; Smet, J.; Haerynck, F.; Eric, Z. P.; Milenova, V.; Gagro, A.; Richter, D.; Chovancova, Z.; Hlavackova, E.; Litzman, J.; Milota, T.; Sediva, A.; Elaziz, D. A.; Alkady, R. S.; El Sayed El Hawary, R.; Eldash, A. S.; Galal, N.; Lotfy, S.; Meshaal, S. S.; Reda, S. M.; Sobh, A.; Elmarsafy, A.; Brosselin, P.; Courteille, V.; De Vergnes, N.; Kracker, S.; Pergent, M.; Randrianomenjanahary, P.; Ahrenstorf, G.; Albert, M. H.; Ankermann, T.; Atschekzei, F.; Baumann, U.; Becker, B. C.; Behrends, U.; Belohradsky, B. H.; Biegner, A. -K.; Binder, N.; Bode, S. F. N.; Boesecke, C.; Boetticher, B.; Borte, M.; Borte, S.; Classen, C. F.; Dirks, J.; Duckers, G.; El-Helou, S.; Ernst, D.; Fasshauer, M.; Fecker, G.; Felgentreff, K.; Foell, D.; Ghosh, S.; Girschick, H. J.; Goldacker, S.; Graf, N.; Graf, D.; Greil, J.; Hanitsch, L. G.; Hauck, F.; Heeg, M.; Heine, S. I.; Henes, J. C.; Hoenig, M.; Holzer, U.; Holzinger, D.; Horneff, G.; Hundsdoerfer, P.; Jablonka, A.; Jakoby, D.; Joean, O.; Kaiser-Labusch, P.; Klemann, C.; Kobbe, R.; Korholz, J.; Kramm, C. M.; Kruger, R.; Landwehr-Kenzel, S.; Lehmberg, K.; Liese, J. G.; Lippert, C. F.; Maccari, M. E.; Masjosthusmann, K.; Meinhardt, A.; Metzler, M.; Morbach, H.; Muller, I.; Naumann-Bartsch, N.; Neubert, J.; Niehues, T.; Peter, H. -H.; Rieber, N.; Ritterbusch, H.; Rockstroh, J. K.; Roesler, J.; Schauer, U.; Scheible, R.; Schmalzing, M.; Schmidt, R. E.; Schneider, D. T.; Schreiber, S.; Schuetz, C.; Schulz, A.; Schulze-Koops, H.; Schulze-Sturm, U.; Schuster, V.; Schwaneck, E. C.; Schwarz, K.; Schwarze-Zander, C.; Sirin, M.; Skapenko, A.; Sogkas, G.; Sparber-Sauer, M.; Speckmann, C.; Steinmann, S.; Stiehler, S.; Tenbrock, K.; von Bernuth, H.; Warnatz, K.; Wasmuth, J. -C.; Weiss, M.; Witte, T.; Wittke, K.; Wittkowski, H.; Zeuner, R. A.; Farmaki, E.; Hatzistilianou, M. N.; Kakkas, I.; Kanariou, M. G.; Kapousouzi, A.; Liatsis, E.; Maggina, P.; Papadopoulou-Alataki, E.; Raptaki, M.; Speletas, M.; Tantou, S.; Goda, V.; Krivan, G.; Marodi, L.; Abolhassani, H.; Aghamohammadi, A.; Rezaei, N.; Feighery, C.; Leahy, T. R.; Ryan, P.; Batzir, N. A.; Garty, B. Z.; Tamary, H.; Aiuti, A.; Amodio, D.; Azzari, C.; Barzaghi, F.; Baselli, L. A.; Cancrini, C.; Carrabba, M.; Cazzaniga, M.; Cesaro, S.; Chinello, M.; Danieli, M. G.; Dellepiane, R. M.; Fabio, G.; Gambineri, E.; Lodi, L.; Lougaris, V.; Marasco, C.; Martire, B.; Marzollo, A.; Milito, C.; Moschese, V.; Pignata, C.; Plebani, A.; Porta, F.; Quinti, I.; Ricci, S.; Soresina, A.; Tommasini, A.; Vacca, A.; Vanessa, C.; Blaziene, A.; Sitkauskiene, B.; Gowin, E.; Heropolitanska-Pliszka, E.; Pietrucha, B.; Szaflarska, A.; Wiesik-Szewczyk, E.; Wolska-Kusnierz, B.; Esteves, I.; Faria, E.; Marques, L. H.; Neves, J. F.; Silva, S. L.; Teixeira, C.; Pereira da Silva, S.; Capilna, B. R.; Guseva, M. N.; Shcherbina, A.; Bobcakova, A.; Ciznar, P.; Gabzdilova, J.; Jesenak, M.; Kapustova, L.; Orosova, J.; Petrovicova, O.; Raffac, S.; Kopac, P.; Allende, L. M.; Antoli, A.; Blanch, G. R.; Carbone, J.; Dieli-Crimi, R.; Garcia-Prat, M.; Gil-Herrera, J.; Gonzalez-Granado, L. I.; Agullo, P. L.; Olbrich, P.; Parra-Martinez, A.; Paz-Artal, E.; Pleguezuelo, D. E.; Rodriguez, N. S.; Sanchez-Ramon, S.; Santos-Perez, J. L.; Solanich, X.; Soler-Palacin, P.; Gonzalez-Amores, M.; Ekwall, O.; Fasth, A.; Bitzenhofer-Gruber, M.; Candotti, F.; Dimitriou, F.; Heininger, U.; Holbro, A.; Jandus, P.; Kolios, A. G. A.; Marschall, K.; Schmid, J. P.; Posfay-Barbe, K. M.; Prader, S.; Reichenbach, J.; Steiner, U. C.; Truck, J.; Bredius, R. G.; de Kruijf- Bazen, S.; de Vries, E.; Henriet, S. S. V.; Kuijpers, T. W.; Potjewijd, J.; Rutgers, A.; Stol, K.; van Aerde, K. J.; Van den Berg, J. M.; van de Ven, A. A. J. M.; Montfrans, J.; Aydemir, S.; Baris, S.; Dogu, F.; Ikinciogullari, A.; Karakoc-Aydiner, E.; Kilic, S. S.; Kiykim, A.; Kokcu Karadag, S. I.; Kutukculer, N.; Ocak, S.; Unal, E.; Boyarchuk, O.; Hilfanova, A.; Kostyuchenko, L. V.; Alachkar, H.; Arkwright, P. D.; Baxendale, H. E.; Bernatoniene, J.; Coulter, T. I.; Garcez, T.; Goddard, S.; Gompels, M. M.; Grigoriadou, S.; Herriot, R.; Herwadkar, A.; Huissoon, A.; Ibberson, L.; Nademi, Z.; Noorani, S.; Parvin, S.; Steele, C. L.; Thomas, M.; Waruiru, C.; Yong, P. F. K.; Bourne, H