Genetic testing of minors for alpha1-antitrypsin deficiency.

BACKGROUND: Alpha(1)-antitrypsin deficiency (AATD) is a genetic disorder primarily affecting the lungs and liver of affected individuals, causing severe panlobular emphysema and cirrhosis. OBJECTIVE: To describe the demographics and feasibility of a home test for AATD in children and adolescents. DESIGN: Case series of parents who test their children for AATD. SETTING: Nonprofit supported program in which participants telephoned or e-mailed requests for alpha(1)-antitrypsin testing. PARTICIPANTS: All persons younger than 18 years whose parents or guardians chose to test for AATD from January 1, 2002, to October 1, 2004. INTERVENTIONS: Home-administered finger-stick blood spot test for alpha(1)-antitrypsin genotype and questionnaire. MAIN OUTCOME MEASURES: The alpha(1)-antitrypsin genotypes and questionnaire responses. RESULTS: The Alpha Coded Testing Study tested 422 children and adolescents with a confidential test for AATD. Testing was suggested by a family member in most (76.7%) of the cases and was responsible for the many carrier (PIMZ and PIMS) genotypes (51.9%) in the study. Interest in testing was equally distributed among all ages. Test confidentiality was seen as an important reason to test (64.1% with a Likert scale score of 4-5 on a 5-point scale). Parents and guardians of the minors suggested that testing benefits (mean [SD] Likert score, 3.5 [1.4] on a 5-point scale) were higher than risks (mean [SD] Likert score, 1.7 [1.2]) (P=.001). CONCLUSION: Parents value genetic testing of their children at risk for AATD when testing can be done in a confidential setting.

Asthma and allergy in alpha-1 antitrypsin deficiency.

This study was designed to determine the prevalence of asthma and atopy, in a large group of subjects with alpha-1 antitrypsin deficiency (AATD) participating in the Alpha-1 Foundation Research Registry. A survey was mailed to all Registry participants (N=2418) and results were collated by AATD phenotype. Participants with PiZZ deficiency were compared to PiMZ and other phenotypes by nonparametric statistics. Responses were collected from 757 participants (31%). Overall 44.6% (N=338) reported MD diagnosed asthma. Wheezing was reported in 76% with respiratory infections, activity and exposure to dusts, fumes, and allergens as common triggers. Across the three groups reported asthma with a history of allergies was reported from 20% to 25%. Wheezing symptoms were significantly less common in the PiMZ group compared with other groups. Of those reporting asthma, 83% of the PiZZ group (n=192) also reported another chronic obstructive pulmonary disease (COPD) diagnosis compared to 48% of the PiMZ group (n=24). Asthma as the only reported diagnosis was three times more prevalent in the PiMZ group compared with the PiZZ group. Although asthma diagnosis is imprecise in the presence of COPD, the high prevalence of wheezing to allergen and irritant exposures with symptoms of atopy suggests that asthma is common in AATD but usually associated with COPD. Those with AATD who are susceptible to asthma require allergy evaluation and aggressive anti-inflammatory strategies as part of their management.

Factors associated with advanced liver disease in adults with alpha1-antitrypsin deficiency.

BACKGROUND & AIMS: Alpha 1 -antitrypsin deficiency (AAT) is an autosomal recessive disease that affects 1 in 2500 persons and might lead to cirrhosis. Our study aim was to characterize the liver disease in AAT and identify factors associated with advanced liver disease. METHODS: A cohort of the Alpha-1 Foundation Registry who reported liver disease was surveyed with a liver disease questionnaire to obtain information related to liver disease, liver transplantation, and AAT phenotype. RESULTS: One hundred sixty-five of the 2175 participants in the registry reported a history of jaundice or liver disease, and 139 (84.2%) completed the questionnaire. Of these, 71.3% were PiZZ, 18.0% were PiMZ, and 5.7% did not know their phenotype. Analysis of 104 participants with a known age of diagnosis included 30 participants diagnosed with liver disease before 18 years, of whom 15 had advanced liver disease defined as liver transplantation or listed for liver transplantation. No differences in age, age at diagnosis, gender, race, phenotype, or infant jaundice were identified. Seventy-four participants were diagnosed after age 18 years, of whom 25 had advanced liver disease. In this group, advanced liver disease was associated with male gender ( P = .006) and a greater mean body mass index ( P = .01), but not with race, Pi phenotype, infant jaundice, diabetes, or hypercholesterolemia. Viral hepatitis was more frequently reported in the nontransplant group (34.7% vs 8.0%, P = .01), and the mean daily alcohol use was significantly greater in this group ( P = .04). CONCLUSIONS: Our results suggest that male gender and obesity but not alcohol or viral hepatitis predispose to advanced liver disease in adults with AAT.