Congenital Plasminogen Deficiency

Synonyms

Hypoplasminogenemia,

Overview

Congenital plasminogen deficiency is a disorder that results in inflamed growths on the mucous membranes, which are the moist tissues that line body openings such as the eyelids and the inside of the mouth. Development of the growths are usually triggered by infections or injury, but they may also occur spontaneously in the absence of known triggers. The growths may recur after being removed.

Symptoms

Congenital plasminogen deficiency most often affects the conjunctiva, which are the mucous membranes that protect the white part of the eye (the sclera) and line the eyelids. A characteristic feature of this disorder is ligneous conjunctivitis, in which a buildup of a protein called fibrin causes inflammation of the conjunctiva (conjunctivitis) and leads to thick, woody (ligneous), inflamed growths that are yellow, white, or red. Ligneous conjunctivitis most often occurs on the inside of the eyelids. However, in about one-third of cases, ligneous conjunctivitis over the sclera grows onto the cornea, which is the clear covering that protects the colored part of the eye (the iris) and pupil. Such growths can tear the cornea or cause scarring. These corneal problems as well as obstruction by growths inside the eyelid can lead to vision loss.

People with congenital plasminogen deficiency may also develop ligneous growths on other mucous membranes, including the inside of the mouth and the gums; the lining of the nasal cavity; and in females, the vagina. Growths on the mucous membranes that line the gastrointestinal tract may result in ulcers. The growths may also develop in the windpipe, which can cause life-threatening airway obstruction, especially in children. In a small number of cases, affected individuals are born with impaired drainage of the fluid that surrounds and protects the brain and spinal cord (the fluid or CSF), resulting in a buildup of this fluid in the skull (occlusive hydrocephalus). It is unclear how this feature is related to the other signs and symptoms of congenital plasminogen deficiency.

Causes

Congenital plasminogen deficiency is caused by an alteration in the plasminogen (PLG) gene. Genes provide instructions for creating proteins that play a critical role in many functions of the body. When a mutation of a gene occurs, the protein product may be faulty, inefficient, or absent. Depending upon the functions of the particular protein, this can affect many organ systems of the body.

Diagnosis

A diagnosis of congenital plasminogen deficiency is based upon identification of characteristic symptoms, a family account of their medical history (anamnesis), a detailed patient history, and a thorough clinical evaluation.

Specific laboratory tests

Can confirm a diagnosis specifically tests that measure the activity of plasminogen, which will be severely deficient in individuals with plasminogen deficiency. Antigen testing which measures the reactivity of plasminogen to a certain antigen may also be used. These tests are available in most clinical coagulation laboratories.

Molecular genetic testin

Can confirm a diagnosis of congenital plasminogen deficiency. Molecular genetic testing can detect alterations in the PLG gene known to cause the disorder, but is available only as a diagnostic service at specialized laboratories.

Treatment

There are no standardized treatment protocols or guidelines for affected individuals. Due to the rarity of the disease, there are no treatment trials that have been tested on a large group of patients. Various treatments have been reported in the medical literature as part of single case reports or small series of patients.

Plasminogene concentartes

The only effective therapies reported in the medical literature are systemic and topical plasminogen concentrates (i.e. replacing the deficient plasminogen in the body) that have led to an improvement in symptoms and prevented recurrence in some people. This includes eye drops that contain plasminogen, which have been effective in treating ligneous conjunctivitis. Plasminogen eye drops, however, are not readily available. Researchers are currently investigating replacement plasminogen to see whether such therapy will clear up existing symptoms and prevent recurrence.

Various therapies have been tried to treat individuals with congenital plasminogen deficiency. Surgical removal of the growths may be beneficial initially, but the growths usually recur. Several medications have been tried including high-dose intravenous corticosteroid treatment, heparin, cyclosporine, azathioprine and hyaluronidase. There is a report of oral contraceptives leading to an increase of plasminogen level in one woman. These therapies have shown no or only limited benefit, or have only been reported in a single person.