| Popis: |
α 1 -Antitrypsin ( α 1 AT) deficiency, a hereditary disorder with an incidence of approx. 1:2000 among Caucasians, is characterized by serum α 1 AT levels of less than 11 pmol/l, a high risk for the development of emphysema and a lower but significant risk for liver dysfunction. A pilot study was initiated to screen for α 1 AT deficiency in the newborn population. Dried blood specimens (DBS) submitted to the New York State Newborn Screening Laboratory were the sample source. The elastase inhibition assay was developed as the initial screen for α 1 AT deficiency based on the fact that α 1 AT is the main physiologic regulator of elastase. Individuals with α 1 AT deficiency have a decreased capacity to inhibit elastase, leaving it free to cleave its substrate, the fluorogenic Ala-Ala-Pro-Ala-7-amido-4-methylcoumarin, thus producing the highly fluorescent product 7-amido-4-methylcoumarin (AMC). A duplicate DBS from fluorescent samples is phenotyped on an agarose isoelectric focusing (IEF) gel. The specificity, sensitivity, low cost and rapid results of the elastase inhibition assay make it well suited as the initial screen for α 1 ATdeficiency. Agarose IEF provides accurate phenotyping results, is less expensive, safer and faster than polyacrylamide IEF, lending itself to newborn screening strategies. Using these methodologies, this study has identified three Pi z newborns in 11,081 screened, an estimated prevalence of 1:3694 in the total (or 1:2019 in the Caucasian) population in New York State. |
