Translated title: ¿Quién disparó sobre el pianista? o la misteriosa enfermedad de Frédéric Chopin

Cystic fibrosis is the most common lethal autosomal recessive disorder among whites. Seventy-two percent of patients with this disease are homozygotes or compound heterozygotes for eight mutations of the cystic fibrosis transmembrane conductance regulator gene on chromosome 7: delta F508, G542X, R553X, W1282X, N1303K, 621 + 1G-->T, 1717-1G-->A, and R117H. We studied the relation between genotype and phenotype in patients from 14 countries. Each of 399 patients who were compound heterozygotes for delta F508 and one other mutation was matched with the delta F508 homozygote of the same sex who was the closest in age from the same center. A paired analysis was performed of the following outcome variables: age at diagnosis, sweat chloride concentration, growth percentiles, pulmonary-function values, chest-film score, pseudomonas colonization, nasal polyps, pancreatic sufficiency, pancreatitis, diabetes mellitus, meconium ileus, distal intestinal obstruction syndrome, rectal prolapse, cirrhosis, and gallbladder disease. The compound heterozygotes having the genotype R117H/delta F508 clearly differed from the age- and sex-matched delta F508 homozygotes: they more often had pancreatic sufficiency (87 percent vs. 4 percent, P < 0.001), were older when the diagnosis was first made (mean [+/- SD] age, 10.2 +/- 10.5 vs. 2.5 +/- 4.3 years; P = 0.002), and had lower sweat chloride concentrations (80 +/- 18 vs. 108 +/- 14 mmol per liter, P < 0.001). There were no statistically significant differences between delta F508 homozygotes and other compound heterozygotes with regard to any variable tested. Prenatal and prognostic counseling for patients with the R117H/delta F508 genotype should include the likelihood that they will have long-term pancreatic sufficiency. Patients with the other genotypes should expect the early onset of pancreatic insufficiency. For none of the genotypes studied can predictions be made about the occurrence of common complications or the severity or course of pulmonary disease.

An increasing percentage of cystic fibrosis (CF) diagnoses are occurring in adulthood. The purpose of this study was to explore how age at diagnosis may be associated with selected disease and sociodemographic characteristics. The 1996 Cystic Fibrosis Foundation (CFF) Patient Registry data were analyzed to test for associations between age at diagnosis and selected variables. All cases involved individuals > or = 18 years who were represented in the CFF Patient Registry for 1996. Patients were assigned to one of two groups: those diagnosed with CF after age 18 years (n = 786) and those diagnosed before 18 years (n = 6,641). In 1996, the incidence of late diagnosis was 7.8%, and the prevalence was 10.9%. The mean age of late diagnosis was 27 years. Respiratory symptoms most frequently led to late diagnosis. Patients receiving a late CF diagnosis were less likely to have alleles for Delta F508. There was no correlation between age at diagnosis and percent predicted FEV(1), although patients in the late-diagnosis group were an average of 10 years older than those in the early-diagnosis group. Late diagnosis was associated with fewer complications, fewer hospitalizations, less oxygen use, fewer courses of home IV treatment, and less enzyme use. Women were most often diagnosed late. Men displayed more diversity in conditions leading to diagnosis. Psychosocially, those patients receiving late diagnoses were more likely to be college graduates, married, and employed full time. For those adults who died in 1996, there was a positive association between their age at diagnosis and age at death. Those patients diagnosed with CF as adults differ, both medically and psychosocially, from those diagnosed at a younger age; these differences have implications for diagnosis, treatment, and education.