1/10. adult alpha1-antitrypsin deficiency.Three adults with alpha 1-antitrypsin deficiency are described. In two of the cases the deficiency was genetically determined (cases 1 and 2), and each demonstrated unusual features of the disease. The liver in case 1 (homozygous) showed cholangiolar hyperplasia which has been recorded only once before. Case 2 (heterozygous) had emphysema and cirrhosis, a combination not previously documented in a heterozygote, in addition to malabsorption. Case 3 represents a case of spurious alpha 1-antitrypsin deficiency with cirrhosis included to emphasize the diagnostic improtance of phenotyping in such cases.- - - - - - - - - - ranking = 1keywords = antitrypsin deficiency, antitrypsin, alpha, deficiency (Clic here for more details about this article) |
2/10. Compound heterozygosity for alpha-1-antitrypsin (S(iiyama) and QO(clayton)) in an Oriental patient.Alpha-1-antitrypsin (alpha1AT) deficiency is extremely rare among Orientals. We treated a 37-year-old man with severe pulmonary emphysema associated with a low serum concentration of alpha1AT. mutation analysis of the alpha1AT gene was performed using a reverse transcription-polymerase chain reaction followed by sequencing. The patient proved to be a compound heterozygote carrying a S(iiyama) deficient allele and a QO(clayton) null allele. This is the first Japanese case of alpha1AT deficiency to arise from such compound heterozygosity in a family with no apparent consanguineous marriage, suggesting that the gene frequency for deficient alleles might be somewhat higher than previously estimated.- - - - - - - - - - ranking = 0.11080950597135keywords = antitrypsin, alpha, deficiency (Clic here for more details about this article) |
3/10. Severe bilateral panlobular emphysema and pulmonary arterial hypoplasia: unusual manifestations of Menkes disease.Menkes disease is an X-linked recessive disorder of copper transport characterized by neurological deterioration, connective tissue, and vascular defects, abnormal hair, and death in early childhood. We report on a patient with Menkes disease in whom severe diffuse emphysema caused respiratory failure and death at 14 months of age. He had severe growth and developmental delays and other typical clinical manifestations of Menkes disease. He developed respiratory problems requiring continuous supplemental oxygen and a progressively enlarging soft tissue mass appeared on the neck. Imaging studies revealed cystic spaces in multiple lobes of the lung consistent with bullous emphysema. The neck mass was determined to be an internal jugular venous aneurysm. At autopsy, extensive emphysematous change was evident. Post-mortem barium injections of the pulmonary arterial system revealed marked dilatation and tortuosity of the preacinar pulmonary arteries and reduced numbers of intra-acinar arteries. Severe emphysema, presumably caused by abnormal elastin due to deficiency of the copper-dependent enzyme lysyl oxidase, may represent an underestimated clinical complication of Menkes disease and should be considered in the differential diagnosis of chronic respiratory disease in these patients.- - - - - - - - - - ranking = 7.1942233536017E-5keywords = deficiency (Clic here for more details about this article) |
4/10. Heterozygous FZ alpha 1 antitrypsin deficiency associated with severe emphysema and hepatic disease: case report and family study.A patient with advanced emphysema and cor pulmonale had the changes of alpha 1 antitrypsin deficiency in a liver biopsy specimen and was shown to have the phenotype PiFZ. This case supports the contention that the F allele of alpha 1 antitrypsin predisposes to the development of emphysema, particularly when it occurs in conjunction with the Z allele.- - - - - - - - - - ranking = 0.85520546276985keywords = antitrypsin deficiency, antitrypsin, alpha, deficiency (Clic here for more details about this article) |
5/10. Molecular basis of the liver and lung disease associated with the alpha 1-antitrypsin deficiency allele Mmalton.Alpha 1-Antitrypsin (alpha 1AT) deficiency is characterized by reduced serum levels of alpha 1AT and a risk for the development of emphysema and liver disease. However, whereas there is an increased risk for emphysema associated with at least 10 alpha 1AT deficiency and null alleles, the hepatic disease is observed only in a subset of these alleles, suggesting that it is not the reduced serum levels of alpha 1AT per se which cause the liver disease. The present study characterizes the alpha 1AT deficiency allele Mmalton, an allele that like the common Z deficiency mutation (Glu342 Lys) is associated with both alpha 1AT deficiency and hepatic disease. Capitalizing on the identification of the homozygous inheritance of the rare Mmalton alpha 1AT deficiency allele, it was demonstrated that although caused by a very different mutation, the Mmalton allele shares with the Z allele the association of liver disease with the same type of abnormalities of alpha 1AT biosynthesis. Cloning of the Mmalton gene and sequence analysis demonstrated that it differs from the normal alpha 1AT M2 allele by deletion of the entire codon (TTC) for residue Phe52. liver biopsy of the Mmalton homozygote revealed inflammation, mild fibrosis, and intrahepatocyte accumulation of alpha 1AT. Evaluation of de novo alpha 1AT biosynthesis in alpha 1AT-synthesizing cells of this individual demonstrated normal levels of alpha 1AT mRNA transcripts but abnormal intracellular accumulation of newly synthesized alpha 1AT at the level of the rough endoplasmic reticulum with consequent reduced alpha 1AT secretion. Finally, retroviral gene transfer of a normal alpha 1AT cDNA and an alpha 1AT cDNA with the Mmalton Phe52 deletion into murine cells demonstrated that the Mmalton cells reproduced the abnormal accumulation of newly synthesized alpha 1AT, thus directly demonstrating that the deletion mutation is responsible for the intracellular accumulation of the newly synthesized alpha 1AT. Thus, not only is the liver disease associated with alpha 1AT deficiency restricted to a subset of alpha 1AT deficiency alleles, it appears to be restricted to those alleles associated with intracellular accumulation of newly synthesized alpha 1AT, suggesting that it is the abnormal intrahepatocyte alpha 1AT accumulation which incites the liver injury.- - - - - - - - - - ranking = 0.67490089149664keywords = antitrypsin deficiency, antitrypsin, alpha, deficiency (Clic here for more details about this article) |
6/10. Emphysema, cirrhosis, and heart block in a young patient with partial alpha 1 antitrypsin deficiency (PiMZ phenotype).Severe lung disease and liver disease are not recognised features of the PiMZ phenotype, which is associated with alpha 1 antitrypsin deficiency. A 31 year old woman with this phenotype was found to have emphysema and complete heart block and showed evidence of hepatic cirrhosis, although her three sisters, all of whom had the same phenotype, were clinically normal. This case supports the possibility of a causal relation between the PiMZ phenotype and chronic lung and liver disease, but an association between alpha 1 antitrypsin deficiency and complete heart block could not be proved in this patient.- - - - - - - - - - ranking = 0.99992805776646keywords = antitrypsin deficiency, antitrypsin, alpha, deficiency (Clic here for more details about this article) |
7/10. The molecular basis of alpha 1-antichymotrypsin deficiency in a heterozygote with liver and lung disease.alpha 1-antichymotrypsin (alpha 1-ACT) is a serine proteinase inhibitor (serpin) with cathepsin g, mast cell chymase and chymotrypsin as target enzymes. We present the case of a middle-aged man with low plasma levels of alpha 1-ACT, asthma with progression to emphysema, and chronic HCV positive liver disease with selective accumulation of alpha 1-ACT in hepatocytes. This secretory defect is analogous to that seen in Pi Z alpha 1-antitrypsin deficiency. The molecular basis of alpha 1-ACT deficiency in this patient has been characterized by direct sequencing of the alpha 1-ACT genes from the patient and his father. A C-->G transversion in exon III causing a 229Pro-->Ala substitution is proposed to cause a conformational change resulting in abnormal transport through the RER. This mutation was found in one of 20 additional tested patients with chronic obstructive lung disease, but in no control. Two additional polymorphisms of the gene have been identified in unrelated healthy individuals with normal plasma alpha 1-ACT levels. The alpha 1-ACT deficiency state may predispose to obstructive lung disease and influence the course of liver disease. Identification of a specific mutation allows identification of heterozygotes for this deficiency allowing future evaluation of its clinical significance.- - - - - - - - - - ranking = 0.17084406031863keywords = antitrypsin deficiency, antitrypsin, alpha, deficiency (Clic here for more details about this article) |
8/10. Case report: emphysematous tuberculous pancreatitis diagnosis by ultrasound and computed tomography.We describe a case of simultaneous tuberculous and pyogenic infection of the pancreas in a 58-year-old Asian man who presented with a pyrexia of unknown origin. There was no evidence of disseminated tuberculosis or immuno-deficiency. The diagnosis was confirmed by ultrasound-guided percutaneous pancreatic aspiration and subsequent progress assessed by sequential computed tomography (CT) and ultrasonography. Complete recovery was achieved on anti-tuberculous chemotherapy without surgical intervention.- - - - - - - - - - ranking = 7.1942233536017E-5keywords = deficiency (Clic here for more details about this article) |
9/10. Relationship between a mild alpha 1 proteinase inhibitor deficiency and respiratory symptoms in a family.A 34-year-old man with pulmonary emphysema was found to have a mild alpha 1 proteinase inhibitor (alpha 1 PI) deficiency. alpha 1 PI status was investigated in this patient and in 35 members of his family. The alpha 1 PI investigations included alpha 1 PI concentration and phenotype and serum inhibitory capacity for trypsin and pancreatic elastase. Fifteen members of the family had alpha 1 PI concentration and inhibitory capacities below the lower normal limit. Five of these members were characterized by the heterozygous MP phenotype and the 10 others by an apparently homozygous M phenotype, in which the M allele may be associated with another unidentified deficiency allele. Two members of the family had alpha 1 PI concentration and elastase inhibitory capacity below the lower normal limits and trypsin inhibitory capacity within the normal range. They were both characterized by the MP phenotype. Six of these 17 members (three of PI type M and three of PI type MP) showed chronic pulmonary symptoms, whereas among the 19 alpha 1 PI non deficient members, no member had a history of significant pulmonary symptoms.- - - - - - - - - - ranking = 0.004452513462456keywords = alpha, deficiency (Clic here for more details about this article) |
10/10. Acute allergic reaction and demonstration of specific IgE antibodies against alpha-1-protease inhibitor.A 44 yr-old female with severe pulmonary emphysema and reduced alpha-1-protease inhibitor (alpha1-PI) serum levels developed an acute anaphylactic reaction following the third intravenous infusion of human alpha1-PI which was administered to prevent the progression of pulmonary emphysema. Specific immunoglobulin e-antibodies against human alpha1-PI could be demonstrated in the patient's serum using an enzyme allergosorbent test. Because of the risk of further severe anaphylactic reaction, the replacement therapy with alpha1-PI was discontinued. physicians should be aware of this rare complication.- - - - - - - - - - ranking = 0.00301564504593keywords = alpha (Clic here for more details about this article) |
| | Next -> |