Alpha1-antitrypsin Deficiency: Lessons Learned from the Bedside to the Gene and Back Again: Diagnosis and Clinical Presentation in aXAT Deficiency

Alpha1-antitrypsin Deficiency: Lessons Learned from the Bedside to the Gene and Back Again: Diagnosis and Clinical Presentation in aXAT DeficiencyDiagnosis and Clinical Presentation in aXAT Deficiency
In 1965, I had collected a larger series of deficient individuals, including 33 probands and their families. The probands had been traced from a variety of files and hospitals and were in no way a representative or an unbiased population sample. They were presented in my PhD thesis as a supplement to Acta Medica Scandinavica.
Based on the laboratory findings available at that time, the new entity was defined by a) an absence of a visible band in the a j-region in paper or agar gel electrophoresis, b) a slightly reduced immu-noelectrophoretic mobility of atAT from deficient individuals, and c) a mean total trypsin inhibitory capacity (TIC) of less than 0.30 mg trypsin inhibited per ml serum. The trypsin inhibitory capacity in normal serum was found to be 1.07 ± 0.12 (SD). Using the trypsin inhibitory capacity (TIC), homozygotes could easily be separated from heterozygotes. It was, however, noted that heterozygotes sometimes during pregnancy, inflammatory conditions or other active processes could increase TIC up to the normal range, a reflection of the acute phase reactant nature of the protein. Alpha!AT in a homozygous individual also increased proportionally but the level never reached the heterozygous range. Today, the diagnosis of o^AT deficiency is still readily made by inspection of an electrophoretic strip but immunochemical quantitation is easily performed and the charge abnormality is confirmed by isoelectric focusing.
Well-known clinical features in axAT deficiency were defined. It was evident that a majority of homozygotes were predisposed to an early onset of predominantly basal emphysema with pronounced tissue destruction. In many cases there was a family history. Quite often infections were absent and the emphysema seemed to be of the primary type. Weight loss was a prominent feature. X-ray findings were dominated by loss or reduction of basal vascular markings. Absence of hypercapnia was typical until very late stages of the disease. Polyglobulia was infrequent. In a few cases, autopsies were performed and Professor F. Linell (Department of Pathology) prepared whole mounted paper sections according to the technique of Gough and Wentworth.

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Tags: emphysema, lung disease, trypsin inhibitory capacity