Alpha-1-antitrypsin phenotypes in patients with renal arterial fibromuscular dysplasia

Fibromuscular dysplasia (FMD) is a significant cause of renal artery stenos is, especially in young females. A rare association between FMD and alpha(1 )-antitrypsin (alpha(1)-AT) deficiency has been reported. We compared the a lpha(1)-AT phenotype distribution in 83 patients with renal arterial FMD wi th those published for Australian populations. alpha(1)-AT phenotyping was performed by isoelectric focusing between pH 4.2 and pH 4.9 on polyacrylami de gels with PiM1M2, PiFM (non-deficiency alleles), PiMS and PiMZ (deficien cy alleles) markers. Following phenotyping, alpha(1)-AT genotyping was perf ormed in 10 patients to confirm the presence of S and/or Z alleles. The phe notype distribution and allele frequencies were similar to those reported f or normal subjects from two Australian populations (72 (86.7%) PiMM phenoty pe, one (1.2%) PiFM, seven (8.4%) PiMS, two (2.4%) PiMZ and one (1.2%) PiSZ ), suggesting that alpha(1)-AT deficiency is not a common aetiological fact or in renal arterial FMD. However, despite FMD being three times less commo n in males than females, and carotid artery dissection being a rare occurre nce, a male with PiMS deficiency phenotype presented with internal carotid artery dissection and had bilateral renal artery FMD. Further, a patient wi th PiSZ deficiency phenotype was one of two sisters with FMD and was more s everely affected than her PiMM normal phenotype sibling. These two patients from the present series together with nine culled from the literature with alpha(1)-AT deficiency phenotype and FMD suggest that the chance combinati on of alpha(1)-AT deficiency and FMD may predispose to severe manifestation s of FMD.