Complement component C6 deficiency in a Spanish family: implications for clinical and molecular diagnosis.

Complement component C6 deficiency is a genetic disease presenting as increased susceptibility to invasive Neisseria meningitidis infections. This disorder has rarely been diagnosed in the Spanish population. In this work we report the immunochemical and molecular characterization of complement C6 deficiency in a Spanish patient showing no detectable functional activity of either the classical or alternative complement pathways and reporting a history of several episodes of meningococcal meningitis. The levels of individual complement components C3, C4, C5, C7, C8 and C9 were within the normal range. However, C6 level was low in the patient's serum as measured by radial immunodiffusion. Exon-specific polymerase chain reaction and sequencing of the C6 gene revealed a previously described homozygous single base deletion in exon 6 (c.821delA), leading to a shift in the reading frame that caused the generation of a downstream stop codon, which, in turn, provoked the truncation of the C6 protein (p.Gln274fs). To our knowledge, this is the first report on the c.821delA mutation in the Spanish population, which has previously only been identified in individuals of African ancestry. Characterization of this mutation was thought interesting in order to elucidate its source and help understand the molecular basis of this uncommon deficiency in our population. Moreover, this report highlights the importance of complement screening in cases of repeated meningococcal infections in order to establish its involvement and to consider adequate clinical recommendations such as prophylactic antibiotics or meningococcal vaccines and, subsequently, for genetic counselling.

[Antibiotic prescription in acute respiratory infections in adults: its variability and appropriateness in 10 Spanish hospitals]. / Prescripción antibiótica en las infecciones respiratorias agudas del adulto: su variabilidad e idoneidad en diez hospitales españoles.

OBJECTIVE: To report the variability in antibiotic prescribing habits for patients diagnosed of non-specified acute respiratory infections (ARI) (according to the International Classification of Diseases 9MC) at Emergency Departments of ten Spanish hospitals, and to evaluate the appropriateness of antimicrobial prescription for such patients, after specifically elaborating some reference patterns for appropriate antimicrobial use. DESIGN: Descriptive study of variability in clinical practice by means of a prospective series of cases. Study of appropriateness by means of elaborating reference standards for appropriate use and comparison with the data from the descriptive study with such standards. DURATION: six months. SETTING: Emergency Department in ten Spanish hospitals from different autonomic communities: Andalucía, Islas Canarias, Castilla-León, Cataluña, Galicia, Madrid, Murcia and Valencia for a 6-month period. PATIENTS: Patients with the diagnosis of community ARI attended at emergency departments. SAMPLE SIZE: 903 cases. INTERVENTIONS: Collection of cases in a unified database with the following variables: age, sex, ARI type, diagnosis of comorbidity, prescribed antimicrobial, hospital admission and type of prescriber. A panel of experts was commissioned to elaborate the gold standards for the appropriate use of antibiotics or the lack of indication for the different locations of ARI. RESULTS: The adjusted proportion of the inappropriate prescription for the group with laryngo-tracheal-influenza-rhinopharyngitis-multiple ARI or non specified infections was 67.9%. CONCLUSIONS: Concerning antibiotic prescription, significant inter-center variability and relevant heterogeneity were observed.