European Epidemiologic Registry of Cystic Fibrosis (ERCF): Comparison of major disease manifestations between patients with different classes of mutations

By August 1997, 11,749 patients with cystic fibrosis had been enrolled in t he European Epidemiologic Registry of Cystic Fibrosis (ERCF). Genotype anal ysis had been performed on 8,963 (76%) of these patients, and the majority had one or two identifiable mutations. Patients with known mutations were c lassified according to the type of mutation (Classes I-V), and were grouped according to the class of mutation on both chromosomes. This resulted in s ix subgroups, including all patients homozygous for Class I (I/I, n = 72), for Class II (II/II, n = 5,020), and for Class III mutations, (III/III, n = 23). Since there were only 23 patients homozygous for Class III mutations, a fourth group was made up of patients who were compound heterozygous for a Class II and III mutation (II/III, n = 265). There were only five patient s homozygous for Class IV mutations, and consequently a fifth group was mad e up of all patients carrying at least one Class IV mutation, regardless of the nature of the mutation on the other chromosome (IV/any, n = 187). None were homozygous for Class V mutations; consequently, a sixth group consist ed of patients carrying at least one Class V mutation (V/any, n = 22). Mean age was highest in groups III/III, IV/any. and V/any (15.6, 16, and 17 years, respectively) as opposed to 12.4 years in group II/II and 13.4 in g roup II/III, but both group III/III and V/any were small, and the confidenc e interval of the mean was large. The percentage of patients receiving panc reatic enzymes was lower in groups IV/any and V/any than in any of the othe r groups. i.e., approximately 50% of patients 18 years or older in both gro ups as opposed to between 90-100% of all other patients regardless of age. The prevalence of diabetes mellitus increased with age from 2.6% in patient s < 18 years to 22.1% in patients 18 years or older in the large group II/I I, but was only 1.5% in patients 18 years or older in group IV/any, Disrega rding the small group III/III, abnormally elevated liver enzymes and/or bil irubin (1.5 x upper normal limit) was much less frequent in group IV/any th an in any of the other groups, both overall and in patients aged 18 years o r more. The course of lung disease appeared to be less dependent on genotyp e than pancreatic function, with only minor differences between groups; how ever. the mean values of both FVC % and FEV1 % were slightly higher in grou p IV/any than all other groups in both younger and older patients. The same was found for the prevalence of some major clinical signs of severe lung d isease, such as clubbing, hyperinflation, and crepitations. Overall mean we ight expressed as an age percentile was markedly higher in group IV/any tha n in any other group, which may be related to the finding of a much lower p revalence of chronic P. aeruginosa infection in patients 18 years or older belonging to group IV/any land V/any) than in any other group. In conclusion, the presence of a class IV mutation appears to offer some de gree of protection against pancreatic insufficiency. diabetes mellitus, and liver disease. We confirmed that lung disease follows a milder clinical co urse in patients with a class IV mutation and that the presence of a class IV mutation land possibly class V) is associated with a delay in the onset of P. aeruginosa infection. (C) 2001 Wiley-Liss. Inc.