ABSTRACT
Alpha-1-antitrypsin deficiency (AATD) is a genetic condition caused by SERPINA1 mutations, which culminates into lower protease inhibitor activity in the serum and predisposes to emphysema. Clinical manifestations of AATD are often associated to ZZ (p.Glu342Lys) and SZ (p.Glu264Val) genotypes and less frequently to rare deficiency or null alleles in heterozygous and homozygous states. We report a case of a 52-year-old woman with bronchiectasis without other potential causes other than an electrophoresis that showed a decrease of alpha-1 globin band and AAT levels below the normal value (78 mg/dl; v.n. 90-200 mg/dl). No S or Z mutation was identified, but sequencing analysis found a novel missense variant Ile74Asn (c.221T > A) in heterozygous state on an M3 allele (Glu400Asp) in the exon 2 of the SERPINA-1gene, probably leading to a dysfunctional protein. This mutation has never been previously identified, and it is interesting to note the association with bronchiectasis in the absence of emphysema.
Subject(s)
Bronchiectasis/genetics , Lung/diagnostic imaging , Mutation, Missense , alpha 1-Antitrypsin Deficiency/genetics , alpha 1-Antitrypsin/genetics , Bronchiectasis/blood , Bronchiectasis/diagnostic imaging , Bronchiectasis/physiopathology , Carbon Monoxide , Female , Forced Expiratory Volume , Genotype , Heterozygote , Humans , Lung/physiopathology , Middle Aged , Pulmonary Diffusing Capacity , Residual Volume , Sequence Analysis, DNA , Tomography, X-Ray Computed , Total Lung Capacity , Vital Capacity , alpha 1-Antitrypsin/blood , alpha 1-Antitrypsin Deficiency/blood , alpha 1-Antitrypsin Deficiency/diagnosis , alpha 1-Antitrypsin Deficiency/physiopathologyABSTRACT
BACKGROUND: Pulmonary mycetoma is a characteristic clinical-radiological lesion due to colonization of aspergillus or candida species in pre-existing pulmonary cavities following a number of diseases. METHODS: We revisited 27 records of such admitted patients (19 M, 8 F; range age 16-27 yrs) analysing diagnostic approach and therapy. Predisposing conditions were sequelae of tuberculosis or lung abscess, bronchiectasis, bullous emphysema, leukaemia/ lymphoma, diabetes mellitus, corticosteroids and/or immunosuppressant administration and antiblastic chemotherapy. All patients had a characteristic chest X-ray and the most common symptoms were cough and haemoptysis. Diagnosis of pulmonary mycetoma was based on positive sputum culture for aspergillus or candida species and/or positive result for aspergillus precipitin test. Eleven patients received only medical treatment, eight pts only a surgical one and eight patients both medical and surgical ones. Antifungal drugs administered were itraconazole or amphotericin B or fluconazole. RESULTS: In the follow-up, six out of eleven patients who had received only medical treatment, cannot be found; five patients or their relatives were interviewed by phone: two of them enjoyed good health and three had died. Sixteen patients underwent thoracic surgery and one of them died because of postsurgical complications. In the follow-up, only nine patients out of this last group were interviewed by phone 2 to 8 years after surgery: seven of them enjoyed good health while two patients had died because of disease not related to pulmonary mycetoma. CONCLUSIONS: Aspergilloma treatment is related to the extension of disease and clinical conditions of patients but surgical resection associated with drug administration, when possible, is the treatment of choice.
