Clinical Chemistry AACC Online Job Center
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

Clinical Chemistry 54: 1399, 2008; 10.1373/clinchem.2008.109868
This Article
Right arrow Extract Freely available
Right arrow Full Text (PDF)
Right arrow Submit an electronic Letter to
the Editor about this paper
Right arrow Alert me when this article is cited
Right arrow Alert me when eLetters are posted
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Google Scholar
Right arrow Articles by Snyder, M. R.
Right arrow Articles by Highsmith, W. E.
PubMed
Right arrow Articles by Snyder, M. R.
Right arrow Articles by Highsmith, W. E., Jr
Related Collections
Right arrow Clinical Case Studies
(Clinical Chemistry. 2008;54:1399.)
© 2008 American Association for Clinical Chemistry, Inc.

Clinical Case Study

Commentary

Melissa R. Snyder and W. Edward Highsmith, Jra

Mayo Clinic, Rochester, MN.

aAddress correspondence to this author at: Mayo Clinic, 9–20 Hilton Building, Rochester, MN, 55905. Fax 507-284-0670; e-mail highsmith.w{at}mayo.edu.

Snyder and Fantz present an interesting case of {alpha}1-antitrypsin (A1AT) deficiency caused by homozygosity for the Z-deficiency allele. Although A1AT deficiency is generally associated with the Z and/or S alleles, other deficiency alleles also occur. The clinical laboratory is faced with the challenge of detecting all clinically relevant alleles in a timely and cost-effective manner. Phenotyping by isoelectric-focusing electrophoresis has been used for many years to identify a wide range of alleles. Although commercial reagent sets are available, phenotyping remains technically demanding. In addition, commercial standards are available only for the S and Z alleles. Recently, DNA-based genotyping has generated interest as an alternative to phenotyping. Because most genotyping assays focus on detection of only the S and Z alleles, however, at least 2 groups of investigators have developed diagnostic algorithms for A1AT deficiency that include quantification, genotyping, and phenotyping (1)(2). The testing begins with measurement of A1AT concentration and genotyping for the S and Z alleles. An A1AT concentration that is lower than expected for the observed genotype suggests the presence of another deficiency allele, a result that requires reflex testing with a method that enables identification of numerous alleles. If phenotyping is selected, in-house comparison samples must be accumulated to permit accurate identification of rare deficiency alleles. Even theoretically, however, it is impossible to collect all potential phenotypes. Alternatively, DNA sequencing can be used to identify rare, deleterious alleles. Although more expensive, sequencing can detect null alleles, is not subject to inference by replacement therapy, and does not require a sample bank of unusual phenotypes. DNA sequencing may become an important component of diagnostic algorithms for A1AT deficiency (3)(4).

Despite efforts to raise awareness of this relatively common genetic disorder, A1AT deficiency remains underdiagnosed. Detailed recommendations for diagnostic testing for symptomatic individuals and asymptomatic individuals who are at increased risk for carrying deficiency alleles have been established (5). Clearly the clinical laboratory will continue to play a central role in the implementation of these recommendations and thus in the diagnosis of A1AT deficiency.


Acknowledgments

Grant/Funding Support: None declared.

Financial Disclosures: None declared.


References

  1. Snyder MR, Katzmann JA, Butz ML, Wiley C, Yang P, Dawson DB, et al. Diagnosis of alpha-1-antitrypsin deficiency: an algorithm of quantification, genotyping, and phenotyping. Clin Chem 2006;52:2236-2242.[Abstract/Free Full Text]
  2. Borhorst JA, Procter M, Meadows C, Ashwood ER, Mao R. Evaluation of an integrative diagnostic algorithm for the identification of people at risk for alpha-1-antitrypsin deficiency. Am J Clin Pathol 2007;128:482-490.[CrossRef][ISI][Medline] [Order article via Infotrieve]
  3. Prins J, van der Meijden BB, Kraaijenhagen RJ, Wielders JPM. Inherited chronic obstructive pulmonary disease: new selective-sequencing workup for alpha-1-antitrypsin deficiency identifies 2 previously unidentified null alleles. Clin Chem 2008;54:101-107.[Abstract/Free Full Text]
  4. Zorzetto M, Russi E, Senn O, Imboden M, Ferrarotti I, Tinelli C, et al. SERPINA1 gene variants in individuals from the general population with reduced {alpha}1-antitrypsin concentrations. Clin Chem 2008;54:1331-1338.[Abstract/Free Full Text]
  5. . American Thoracic Society, European Respiratory Society. American Thoracic Society/European Respiratory Society statement: standards for the diagnosis and management of individuals with alpha-1-antitrypsin deficiency. Am J Respir Crit Care Med 2003;168:818-900.[Free Full Text]




This Article
Right arrow Extract Freely available
Right arrow Full Text (PDF)
Right arrow Submit an electronic Letter to
the Editor about this paper
Right arrow Alert me when this article is cited
Right arrow Alert me when eLetters are posted
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Google Scholar
Right arrow Articles by Snyder, M. R.
Right arrow Articles by Highsmith, W. E.
PubMed
Right arrow Articles by Snyder, M. R.
Right arrow Articles by Highsmith, W. E., Jr
Related Collections
Right arrow Clinical Case Studies

HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS