Diagnostic flow chart for targeted detection of alpha1-antitrypsin deficiency.
BACKGROUND
Alpha1-antitrypsin (AAT) deficiency is under-recognized, probably because many individuals affected show no clinical impairment. The targeted detection is a tool to increase its recognition.


METHODS
We prospectively submitted to AAT serum levels determination, phenotyping and, if doubtful, genotyping: (i) patients with the early onset of emphysema, emphysema in absence of recognized risk or pneumothorax (path P), antineutrophil cytoplasm antibodies (ANCA) positive vasculitis (path V), cervical artery dissection (path A), Periodic acid-Schiff (PAS) positive bodies in the liver cell or unexplained abnormal transaminase level (Path L) [index cases: IC] and (ii) subjects with low-serum alpha1-globulin (path e) and close relatives of patients with AAT deficiency (path r) [non index cases: NIC]. We determined and compared gender, age, AAT serum levels values, the ratio between AAT deficiency subjects identified and all subjects examined (identified/examined). Receiver operating characteristic (ROC) curve was plotted to find the best threshold for AAT serum levels.


RESULTS
Two hundred and eighty-five individuals were examined and 211 with AAT deficiency identified: 66 were IC and 145 NIC. The ratio identified/examined resulted 0.74. A serum level of 120 mg/dL was able to identify AAT deficiency with a specificity of 73% and a sensitivity of 97%. IC showed male prevalence (P=0.005), more advanced age (P=0.02), lower AAT serum levels (P=0.008).


CONCLUSIONS
Our protocol is effective to detect AAT deficiency in a selected population. About 120 mg/dL (nephelometric method) is a reliable AAT serum level cut-off for selecting subjects/patients to submit to phenotype or genotype; as compared to NIC, IC are older, mostly male and with lower AAT serum levels.
Corda
Luciano
L
Prima Divisione di Medicina, Spedali Civili, P.le Spedali Civili no. 1, 25123 Brescia, Italy. medicinarespiratoria@libero.it
Bertella
Enrica
E
Pini
Laura
L
Pezzini
Alessandro
A
Medicina
Daniela
D
Boni
Enrico
E
Guerini
Michele
M
Trivella
Simona
S
Grassi
Vittorio
V
Tantucci
Claudio
C
D000328:Adult; D000368:Aged; D000465:Algorithms; D005260:Female; D005838:Genotype; D006801:Humans; D008099:Liver / Q000737:chemistry*; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D012680:Sensitivity and Specificity; D017678:Sex Distribution; D019896:alpha 1-Antitrypsin Deficiency / Q000097:blood / Q000175:diagnosis* / Q000235:genetics