Plasminogen Deficiency and Related Disorders

Plasminogen deficiency is a rare autosomal recessive or dominant disorder marked by reduced levels or function of plasminogen, the zymogen precursor of the fibrinolytic enzyme plasmin. Impaired conversion of fibrin to soluble degradation products leads to persistent fibrin deposition in mucosal tissues, manifesting most commonly as ligneous conjunctivitis, gingival enlargement, ligneous periodontitis and, in severe cases, hydrocephalus or membranous complications in the respiratory and genitourinary tracts. Two major clinical subtypes are recognised: type I, characterised by diminished plasminogen antigen and activity, and type II, marked by normal antigen levels but reduced functional capacity. Beyond its classic ophthalmic and periodontal presentations, plasminogen deficiency carries implications for wound healing, thrombotic risk and developmental anomalies, reflecting the enzyme’s roles in extracellular matrix remodelling, cell migration and angiogenesis. Current management includes topical or systemic plasminogen replacement, adjunctive antimicrobial or anti-inflammatory therapies and multidisciplinary supportive care. Advances in genetic diagnostics and mechanistic studies are reshaping our understanding of genotype–phenotype relationships, guiding personalised approaches to diagnosis, prognostication and treatment.

Research from Nature Portfolio

Recent work has employed next-generation sequencing to unravel the genetic architecture of plasminogen deficiency in affected families, identifying multiple novel PLG variants with predicted pathogenicity. Detailed genotype–phenotype correlation studies revealed that while certain mutations correlate with the classic ligneous phenotype, others may act as susceptibility factors for thrombotic or developmental disorders. Functional assays confirmed that these variants impair plasmin generation and fibrinolytic capacity, emphasising the multifactorial nature of clinical outcomes. This research underscores the value of comprehensive genetic and functional profiling to refine risk assessment and inform targeted monitoring strategies in individuals with plasminogen pathway defects.

Plasminogen Deficiency and Related Disorders publication trend

The graph below shows the total number of articles in plasminogen deficiency and related disorders across all publications each year (not limited to Nature Index journals).

Technical terms

Plasminogen: Inactive precursor of plasmin, synthesised in the liver, essential for fibrin clot degradation.

Plasmin: Active serine protease that dissolves fibrin matrices and modulates extracellular matrix remodelling.

Fibrinolysis: Enzymatic process by which fibrin clots are degraded to soluble fragments, restoring vessel patency and tissue homeostasis.

Ligneous conjunctivitis: Chronic pseudomembranous inflammation of the conjunctiva due to fibrin deposition in plasminogen deficiency.

Urokinase-type plasminogen activator (uPA): Serine protease that converts plasminogen to plasmin, initiating the fibrinolytic cascade.

References

1. Loss of tissue-type plasminogen activator causes multiple developmental anomalies. Brain Communications (2024).
2. The Unravelling of the Genetic Architecture of Plasminogen Deficiency and its Relation to Thrombotic Disease. Scientific Reports (2016).
3. Ligneous periodontitis exacerbated by Behçet’s disease in a patient with plasminogen deficiency and a stop-gained variant PLG c.1468C > T: a case report. BMC Oral Health (2023).