plasminogen deficiency type 1
Thursday 17 April 2008
Plasminogen (plg) deficiency has been classified as (i) hypoplasminogenemia or ’true’ type I plasminogen deficiency (#16849641#), and (ii) dysplasminogenemia, also called type II plasminogen deficiency. Both forms, severe hypoplasminogenemia and dysplasminogenemia, are not causally linked to venous thrombosis.
Type I plasminogen deficiency is caused by mutation in the gene encoding plasminogen (PLG) MIM.173350).
Congenital plasminogen deficiency is a rare autosomal recessive disorder characterized clinically by chronic muscosal pseudomembranous lesions consisting of subepithelial fibrin deposition and inflammation.
The most common clinical manifestation is ligneous (’wood-like’) conjunctivitis, a redness and subsequent formation of pseudomembranes mostly on the palpebral surfaces of the eye that progress to white, yellow-white, or red thick masses with a wood-like consistency that replace the normal mucosa.
The lesions may be triggered by local injury and/or infection and often recur after local excision.
Pseudomembranous lesions of other mucous membranes often occur in the mouth, nasopharynx, trachea, and female genital tract. Some affected children also have congenital occlusive hydrocephalus. A slightly increased female:male ratio has been observed (1.4:1 to 2:1).
Type I plasminogen deficiency is characterized by decreased serum plasminogen activity, decreased plasminogen antigen levels, and clinical symptoms, whereas type II plasminogen deficiency, also known as ’dysplasminogenemia,’ is characterized by decreased plasminogen activity with normal or slightly reduced antigen levels. Patients with type II deficiency are usually asymptomatic.
Ligneous conjunctivitis and pseudomembranous formation has only been associated with type I plasminogen deficiency. Presumably, normal amounts of plasminogen antigen with decreased activity, as seen in type II, is sufficient for normal wound healing.
Dysplasminogenemia does not lead to a specific clinical manifestation and probably represents only a polymorphic variation in the general population, mainly in Asian countries.
Severe hypoplasminogenemia is associated with compromised extracellular fibrin clearance during wound healing, leading to pseudomembraneous (ligneous) lesions on affected mucous membranes (eye, middle ear, mouth, pharynx, duodenum, upper and lower respiratory tract and female genital tract).
Ligneous conjunctivitis is by far the most common clinical manifestation. More than 12% of patients with severe hypoplasminogenemia exhibit congenital occlusive hydrocephalus.
In milder cases of ligneous conjunctivitis, topical application of plg-containing eye drops, fresh frozen plasma, heparin, corticosteroids or certain immunosuppressive agents (such as azathioprine) may be more or less effective.
Oral treatment with sex hormones was successful in two female patients with ligneous conjunctivitis. In severe cases with possibly life-threatening multi-organ involvement, true therapeutic options are not available at present.
ligneous vaginitis (#17889676#)
congenital occlusive hydrocephalus (12% of severe hypoplasminogenemia) (#17503307#, #10360521#)
acute sensorineural hearing loss and vertigo (#16500059#)
pulmonary involvement (#12719968#)
primary pulmonary hypertension (#8358126#)
The plg-knockout mouse is a useful tool to study the many different properties of plg in a variety of settings, such as wound healing, tissue repair and tissue remodeling, virulence and invasiveness of certain bacteria in the human host, tumor growth and dissemination, as well as arteriosclerosis.
hereditary defects in fibrinolysis
Schuster V, Hügle B, Tefs K. Plasminogen deficiency. J Thromb Haemost. 2007 Dec;5(12):2315-22. PMID: #17900274#