Journal of Rare Disorders: Diagnosis & Therapy

PI*ZMwurzburg: A Novel Rare Genotype of Severe Alpha 1-Antitrypsin Deficiency

Background and Context: Alpha 1-antitrypsin deficiency (AATD) is a rare autosomal codominant disease typically leading to early development of emphysema due to imbalance between neutrophilic proteases and Alpha 1-antitrypsin (AAT) antiprotease effect. AAT polymerogenic variants, as Z, or rare Mmalton and Mwurzburg, can also contribute to liver fibrosis.

Case report: We describe a novel rare genotype of severe AATD identified in a 16-year-old asthmatic never-smoker male suffering for spontaneous left-apical pneumothorax, recurrent pneumonias and hepatic fibrosis. Suspicion of AATD was posed after a low alpha 1 serum electrophoretic band (total alpha 1 proteins 2.5%, reference value 2.9-4,9%) was detected. AAT blood concentration resulted 51.8 mg/dL (reference value 90-200 mg/dL).

Discussion: Genetic analysis demonstrated the presence in heterozygote fashion of two deficient variants: Z (p.E366K, c.1096G>A, rs28929474) and Mwurzburg (p.P393S, c.1177C>T, rs28931570). Therefore, genotype resulted PI*ZMwurzburg. Despite severe AATD, since the very young age of the patient, the possibility to avoid risk factors as smoke and alcohol intake, and the moderate pulmonary clinical involvement, a strict follow up without AAT augmentation therapy was applied.

Conclusion: When AATD is suspected, correct genotype should be always achieved through molecular analysis to personalize clinical-therapeutic management of this rare disorder.

Author(s):

Claudio Tirelli*, Davide Piloni, Francesca Mariani, Stefania Ottaviani, Ilaria Ferrarotti and Angelo Guido Corsico

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