V Kotke

[The German registry of individuals with alpha-1-antitrypsin deficiency--a source for research on patient care].

BACKGROUND alpha-1-Antitrypsin deficiency (AATD) is a rare condition with a prevalence of about 1/4000 individuals in Germany. The clinical manifestations are the early development of pulmonary emphysema or of liver cirrhosis. The low prevalence of AATD suggested the establishment of a registry with the aim to learn more details about the natural history and the quality of care for these patients. METHODS, PATIENTS, RESULTS Since 2004 the German registry for individuals with AATD is maintained in Marburg. Up to May 2008, 548 individuals were registered, 455 with the genotype PiZZ and 46 with PiSZ. The age range of the registered individuals extends from 2 to 82 years (mean 55, SD 20; men 54 [SD 19] years, women 55 [SD 21] years). Most patients are affected by chronic obstructive pulmonary disease (COPD, distribution to the GOLD stages: GOLD I = 16 %, GOLD II = 30 %, GOLD III = 33 %, GOLD IV = 21 %). Currently 109 subjects are under substitution therapy. The time period between the first symptom and the establishment of the correct diagnosis was on average 5.6 years. CONCLUSIONS The data of the registry allow a detailed characterisation of the natural course of the disease and the levels of the patient care.

Alpha-2-Makroglobulin-Serumspiegel bei Patienten mit Alpha-1-Antitrypsin-Mangel

Background and objectives Alpha-2 Macroglobulin (A2M) is a plasma protein with proteolytic effects on many proteases. In patients with an inborn alpha-1 antitrypsin deficiency (AATD) the homeostasis between proteases and antiproteases is disturbed. The aim of this study was to compare the levels of AAT and A2 M in patients and controls. We hypothesized that in patients with AATD A2 M levels are elevated. Methods Patients with AATD (polymorphism Pi*ZZ, Pi*SZ, Pi*MZ and rare gene variants) as well as healthy volunteers (Pi*MM) were tested for A2 M and AAT levels. The concentration of the proteins was measured by nephelometry. The polymorphisms Pi*Z and Pi*S were detected by polymerase chain reaction (PCR), the rare genetic variants were identified by sequencing. Results In our study, a total of 291 individuals were included. It could be shown that a significant increase in A2 M levels in the serum could be observed in the presence of a gene polymorphism (Pi*ZZ) and an alpha-1 antitrypsin serum level < 50 mg/dl compared to the healthy volunteers. Conclusions In this study, an inverse correlation between the serum levels of AAT and A2 M was found in the presence of a gene polymorphism (Pi*ZZ). Further studies are necessary to elucidate the clinical significance of increased A2 M serum levels in patients with severe AAT deficiency Pi*ZZ and rare gene variants whose AAT serum level is < 50 mg/dl.