Rare Disease Report

Chapter 12: Congenital Plasminogen Deficiency

Congenital plasminogen deficiency type I is a rare genetic disorder in which a person lacks plasminogen, a precursor to the enzyme, plasmin. Plasmin is involved in the degradation of various plasma proteins.

One of these plasma proteins is fibrin. In plasminogen deficiency type I, the reduced levels of plasmin means there is an abnormal accumulation of fibrin that, in turn, causes inflammation and abnormal growths in mucus membranes throughout the body.

Congenital plasminogen deficiency type I is an autosomal recessive genetic condition. A child must receive 2 copies of the mutation in order to be affected. Therefore, if both parents are carriers, there is a 1-in-4 chance their child will have the plasminogen deficiency.

It is an extremely rare condition, with an incidence of 1 to 2 persons per million individuals. These numbers plus the wide variation in symptoms observed with the condition mean there is still much to learn about this disease.


The signs and symptoms of plasminogen deficiency type I vary greatly among patients. They may begin early in childhood or not appear until adulthood.

The most common clinical manifestations are ligneous conjunctivitis (80%of patients) and ligneous gingivitis (34%). Ligneous conjunctivitis is a chronic, recurrent conjunctivitis characterized by wood-like, fibrinous pseudomembranes usually located on the gums or eyelid surfaces. The lesions progress to form white, yellow-white, or thick red masses that replace normal mucosa. The fibrous lesions are often painful and can compromise organ function and lead to emergency department visits because of a collapsed lung, kidney failure, or impaired vision.

Fibrous growth may also involve the respiratory tract, ears, vagina, or gastrointestinal tract. Hydrocephalus has also been reported in 12% of patients.


There is currently no approved therapy for plasminogen deficiency, and treatment depends on the fibrous lesions’ location and how much discomfort that provide. Surgery to remove the lesions is commonly performed, but growths tend to recur. As a result, patients may undergo more than 10 or 20 eye surgeries. A major hindrance to performing surgery is that the disease itself is due to an inability to properly manage fibrin and fibrin is part of the healing process following surgery.

There are currently 2 treatments in development that may help patients with plasminogen deficiency: one is plasminogen-containing eye drops to treat ligneous conjunctivitis, which is currently in a phase 2/3 clinical trial, and the other is a plasminogen-replacement therapy, also in a phase 2/3 clinical trial.
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