Type 1 plasminogen deficiency

Other Names: Hypoplasminogenemia;Congenital plasminogen deficiency;plasminogen deficiency, type I

Type 1 plasminogen deficiency is a genetic condition associated with inflammed growths on the mucous membranes, the moist tissues that line body openings such as the eye, mouth, nasopharynx, trachea, and female genital tract. The growths may be triggered by local injury and/or infection and often recur after removal.

Epidemiology

The prevalence of congenital plasminogen deficiency has been estimated at 1.6 per one million people. This condition is believed to be underdiagnosed, because growths in one area are often not recognized as being a feature of a disorder that affects many body systems. Mild cases likely never come to medical attention.

Cause

Congenital plasminogen deficiency is caused by mutations in the PLG gene. This gene provides instructions for making a protein called plasminogen. Enzymes called plasminogen activators convert plasminogen into the protein plasmin, which breaks down another protein called fibrin. Fibrin is the main protein involved in blood clots and is important for wound healing, creating the framework for normal tissue to grow back. Excess fibrin is broken down when no longer needed, and the new, more flexible normal tissue takes its place.

PLG gene mutations can decrease the amount of plasminogen that is produced, its function, or both. When the mutations affect plasminogen levels as well as the activity of the protein, affected individuals may be said to have type I congenital plasminogen deficiency, characterized by the ligneous growths previously described. People with mutations that result in normal levels of plasminogen with reduced activity are said to have type II congenital plasminogen deficiency or dysplasminogenemia. This form of the condition often has no symptoms.

A reduction in functional plasminogen results in less plasmin to break down fibrin, leading to a buildup of fibrin. The excess fibrin and the resulting inflammation of the tissue result in the inflamed woody growths characteristic of congenital plasminogen deficiency.

It is unclear why the excess fibrin builds up in the mucous membranes but does not usually result in abnormal clots in the blood vessels (thromboses). Researchers suggest that other enzymes in the blood may also break down fibrin, helping to compensate for the reduced plasminogen levels.

Inheritance

Autosomal recessive inheritance, a 25% chance

This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.

Signs and 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 cerebrospinal 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.

For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed. 80%-99% of people have these symptoms

• Abnormality of vision(Abnormality of sight)
• Decreased level of plasminogen

30%-79% of people have these symptoms

• Gingival overgrowth(Gum enlargement)
• Gingivitis(Inflamed gums)

5%-29% of people have these symptoms

• Abnormal fallopian tube morphology
• Abnormality of the middle ear
• Abnormality of the ovary(Abnormality of the ovaries)
• Abnormality of the respiratory system
• Abnormality of the skin
• Cervicitis(Uterine cervix inflammation)
• Dandy-Walker malformation
• Duodenal ulcer
• Hydrocephalus(Too much cerebrospinal fluid in the brain)
• Nephritis(Kidney inflammation)
• Nephrolithiasis(Kidney stones)
• Periodontitis

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 type I. 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 testing 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 is currently no established approach to treatment of type 1 plasminogen deficiency. However, some cases of ligneous conjunctivitis, the most common disease manifestation, have been successfully treated using a combination of surgery and plasminogen administration.

Surgery alone to remove the eye growths can be a temporary fix; however, irritation secondary to surgery can result in recurrence. Other therapies that have been used in reports with varying degrees of success include corticosteroids, immunosuppressants (Cyclosporine), blood thinners (heparin), alpha-chymotrypsin (digestive enzyme), plasma infusion (white blood cells), and anti-virals. Clinical trials regarding the use of plasminogen replacement therapy are ongoing.

NIH genetic and rare disease info

• NIH info on Type 1 plasminogen deficiency

Type 1 plasminogen deficiency is a rare disease.

Type 1 plasminogen deficiency Resources
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