We tested to an alpha level of 5% for the alternative hypothesis: median 1 > median 2 > 0ellip; > median 6. A P-value of smaller than 0·05 indicates that there is a significant improvement in diagnostic delay as time progresses. Of the 13 708 patients, 12 340 (90%) were reported to be alive at the time of documentation,

while 1084 (7·9%) had died and 284 (2·1%) were lost to follow-up. A total of 6017 patients (43·9%) had only been registered at one time-point, 3001 patients (21·9%) had one follow-up and 4690 patients (34·2%) had two or more follow-up documentations; 5609 patients (40·9%) had been first reported or updated within the last 2 CP-690550 cost years. Predominantly antibody disorders ICG-001 in vitro represent the largest main disease category with 7567 patients or 55·2% of all patients. This category also contains the most frequently reported single diseases: CVID (21%), sIgA deficiency (10·4%), IgG subclass deficiency (6·5%) and agammaglobulinaemias (5·9%). The complete distribution of patients is shown in Table 1. Although PID are, by definition, genetic diseases, the genetic cause is still unknown in many patients. In our database, a genetic defect was known in 36·2% of all patients. Information on the affected gene

was lacking particularly in antibody disorders, where it was indicated for only 918 of 7567 patients (12·1%) (Table 1). In total, 1210 patients (8·8%) were reported to have a consanguineous background. Consanguinity was particularly high in T cell deficiencies (306 patients, 28·7%) and autoimmune many and immunedysregulation syndromes (110 patients, 21·4%) (Table 1).

A total of 2532 patients (18·5%) were reported to be familiar cases (i.e. other members in family also presented with a PID). The rate of familiar cases was particularly high among complement deficiencies (393 patients, 61·8%), defects in innate immunity (42 patients, 39·3%) and autoimmune and immunedysregulation syndromes (170 patients, 33·1%) (Table 1). The median of the total distribution was 17 years. Almost 25% of all patients were younger than 10 years (see Table 2). The age distribution varied considerably by disease category. Antibody and complement deficiencies had a particularly high share of older patients, with 35·1% and 50·2% in the group between 34 and 98 years, respectively. Conversely, the proportion of patients in the group between 0 and 9 years was particularly high in T cell deficiencies (47·9%) and autoinflammatory syndromes (56·3%). A total of 8032 (58·6%) of patients were male and 5676 (41·4%) female. If all patients with diseases showing X-chromosomal inheritance are excluded (1714), there are still more male (6355; 53%) than female (5639; 47%) patients. Considering the age distribution (frequencies) among male and female living patients in particular (Fig.