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Background: Knowledge of the frequency of rare SERPINA1mutations could help in the management of alpha1 antitrypsin deficiency (AATD). The present study aims to assess the frequencies of rare and null alleles and their respiratory and hepatic pathogenicity. Methods: This is a secondary analysis of a study that evaluated the viability of the Progenika diagnostic genotyping system in six different countries by analyzing 30,827 samples from cases of suspected AATD. Allele-specific genotyping was carried out with the Progenika A1AT Genotyping Test which analyses 14 mutations in buccal swabs or dried blood spots samples. SERPINA1gene sequencing was performed for serum AAT-genotype discrepancies or by request of the clinician. Only cases with rare mutations were included in this analysis. Results: There were 818 cases (2.6%) carrying a rare allele, excluding newly identified mutations. All were heterozygous except for 20 that were homozygous. The most frequent alleles were the M-like alleles, PI*Mmaltonand PI*Mheerlen. Of the 14 mutations included in the Progenika panel, there were no cases detected of PI*Siiyama, PI*Q0granite fallsand PI*Q0west. Other alleles not included in the 14-mutation panel and identified by gene sequencing included PI*Mwürzburg, PI*Zbristol, and PI*Zwrexham, and the null alleles PI*Q0porto, PI*Q0madrid, PI*Q0brescia, and PI*Q0kayseri. Conclusions: The Progenika diagnostic network has allowed the identification of several rare alleles, some unexpected and not included in the initial diagnostic panel. This establishes a new perspective on the distribution of these alleles in different countries. These findings may help prioritize allele selection for routine testing and highlights the need for further research into their pathogenetic role.

Chest wall tuberculosis is a rare entity and its clinical presentation may resemble a pyogenic abscess or chest wall tumor. The role of surgery in the diagnosis and treatment of chest wall tuberculosis is still controversial. During a 6-year period (1997-2002), six cases with cold abscesses of chest wall were managed in our clinic. Clinical presentation, diagnostic workup, treatment strategies, and results of medical and surgical treatment were retrospectively reviewed. There were four male and two female patients. All but one had a fluctuating and abscess-like chest wall mass. Pleura and mediastinal or chest wall lymph nodes were also involved in three patients. Before the debridement and abscess drainage, the diagnosis was not confirmed in any of our patients except one. All received a four-drug antituberculous regimen for 6-12 months postoperatively and improved clinically and radiologically. Surgical intervention and histological examination are usually necessary for the treatment and to confirm the diagnosis in chest wall tuberculosis. Antituberculous medical treatment and adjunctive surgery are quite effective in this process.