Lactic acid dimer: an artifact in the gas chromatographic analysis of urine with massive lactic acid aciduria.

although the phenotypic IEF analysis was in agreement with her diminished pulmonary function. Geno-typing for S and Z alleles has become a routine laboratory test. However, it is important to realize that these tests might give misleading results, as shown in this case. One should always be aware of the possible presence of alleles such as M Heerlen if a standard genotypic analysis is not in agreement with serum AAT values and/or IEF analysis. Recognition and awareness of these caveats warrants reliable molecular genotyping test results. If an allelic variation such as M Heerlen is suspected in an individual, it is important to realize that there are many possible variants that may also account for discrepancies such as those reported here (7). To detect any of these variants one could use an aselective prescreening method to detect the presence of mutations per se. A variety of methods to detect single nucleotide poly-morphisms and small deletions or insertions are currently available, e.g., single strand conformation poly-morphism analysis, heteroduplex analysis, and enzymatic mutation detection. If an aberration is found, the exact mutation can be identified by sequence analysis. The alternative would be to sequence entire genes or coding regions. However, AAT gene mutations are all named after the places where they were initially described (8). Therefore, the geographic origin of an individual might give a clue to the nature of the possible variation in question. In fact, it turned out that the grandparents of the propositus used to live in the town of Heerlen. To our knowledge, the combination of a Z and a M Heerlen allele has not been described before now. As can be expected from the AAT concentration , the pulmonary function in the two sisters is affected to a degree similar to that seen in Pi ZZ individuals. One can only speculate about potential liver involvement at a young age because deposition of AAT in hepatocytes does not seem to complicate M Heerlen homozygosity. The risk of juvenile cirrhosis in Pi ZZ individuals, as a result of deposition of AAT in inclusion bodies, is well known. Compound heterozygotes for Z and M Heerlen might have an intermediate risk for liver involvement. Competitive assay to improve the specificity of detection of single-point mutations in ␣1-anti-trypsin deficiency. and simple diagnosis of the two common ␣-1-proteinase inhibitor deficiency alleles Pi*Z and Pi*S by DNA analysis. detection of the two common ␣ …