Serpinopathy with loss of serpin function

Serpinopathy with loss of serpin function is a group of rare genetic disorders caused by mutations in genes encoding serine protease inhibitors (serpins) that result in reduced or absent functional serpin protein. Serpins are a superfamily of proteins that regulate critical proteolytic cascades throughout the body, including those involved in coagulation, inflammation, complement activation, and tissue remodeling. When serpin function is lost, the corresponding protease activity becomes unregulated, leading to tissue damage in affected organ systems. The specific clinical manifestations depend on which serpin gene is affected; for example, loss of alpha-1 antitrypsin (SERPINA1) function leads to unopposed neutrophil elastase activity causing emphysema and liver disease, while loss of antithrombin (SERPINC1) function results in a prothrombotic state. Other serpinopathies with loss of function may affect the nervous system, skin, or immune regulation depending on the specific serpin involved. This category is distinguished from serpinopathies caused by toxic gain-of-function mechanisms (such as polymerization and intracellular accumulation of misfolded serpin proteins). In loss-of-function serpinopathies, the primary pathology arises from deficiency of the inhibitory activity rather than from protein aggregation. Diagnosis typically involves measuring serpin protein levels and functional activity in blood or tissues, combined with genetic testing of the relevant serpin gene. Treatment approaches vary by the specific serpin deficiency and may include protein replacement therapy (as in alpha-1 antitrypsin augmentation therapy), anticoagulation for thrombotic serpinopathies, or supportive and symptomatic management. Gene therapy approaches are under investigation for some forms. Management is generally lifelong and requires multidisciplinary care.

Inheritance

Variable

Can be inherited in different ways depending on the underlying gene

Age of Onset

Variable

Can begin at different ages, from infancy through adulthood

Source: openFDA + DailyMed · NDA / BLA labels with structured indications · refreshed weekly

Source: ClinicalTrials.gov · synced daily · phases, status, and PI names normalized at ingest

Source: NPI Registry + PubMed · trial PI roles cross-referenced with ClinicalTrials.gov · ranked by match score (publications + PI activity + community signal)

Source: NORD Rare Disease Centers + NIH Undiagnosed Diseases Network (UDN) · centers verified active within last 12 months

Source: PubMed + NIH RePORTER + openFDA + clinical-journal RSS · last 30 days · disease-tagged at ingest by AI extraction with human QC

Common questions about Serpinopathy with loss of serpin function