Alpha 2-Antiplasmin Deficiency
Pattern of Inheritance
Congenital deficiency of alpha 2-antiplasmin follows an autosomal recessive pattern of inheritance. A history of consanguineous marriage is often present in families of patients with homozygous deficiency.
Several allelic variants have been described.7
a. The alpha 2-antiplasminEnschede is characterized by dysfunctional full-length alpha 2-antiplasmin at normal plasma concentrations (antigen 100% with activity 3%). This variant results in a qualitative defect in homozygous patients due to an alanine insertion near the active site of the molecule (between nucleotides 355 and 356 in exon 10).
b. The alpha 2-antiplasminOkinawa is a quantitative defect in homozygous patients with both antigen and activity <1%. The glutamine deletion results in a structural alteration of the protein and the intracellular transport from the rough endoplasmic reticulum to the Golgi apparatus is impaired with subsequent degradation by proteasomes.
c. The alpha 2-antiplasminNara is also a quantitative defect in homozygous patients with both antigen and activity <1%. The frameshift mutation due to cytidine insertion at codon 480 in exon 10 also impairs intracellular transport, thus affecting protein secretion.
d. The alpha 2-antiplasminParis Trousseau is a result of splicing donor mutation in intron 2 in which a truncated protein is synthesized. The antigen level is <5% and activity at 15% in homozygous patients.
e. The alpha 2-antiplasminVal 384 Met is a valine substitution by methionine at site 384, resulting in multimerization and reduction of hepatic excretion.
f. An intron 6 splicing donor site G to A mutation resulting in heterozygous quantitative deficiency.9
g. Deletion of cytosine at codon 399 resulting in severe bleeding tendency with undetectable antigen and functional levels.10
Additional details of the disorder can be found on the Online Mendelian Inheritance in Man® (OMIM) website.Next