Type 1 plasminogen deficiency

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Disease Profile

1-9 / 1 000 000

US Estimated

Europe Estimated

Age of onset

All ages

ICD-10

L90.5

Inheritance

Type 1 plasminogen deficiency is inherited in an autosomal recessive manner. This means that to be affected, a person must have a mutation in both copies of the responsible gene in each cell.^[2] Affected people inherit one mutated copy of the gene from each parent, who is referred to as a carrier. Carriers of an autosomal recessive condition typically do not have any signs and symptoms (they are unaffected). When 2 carriers of an autosomal recessive condition have children, each child has a:

25% (1 in 4) chance to be affected,
50% (1 in 2) chance to be an unaffected carrier, like each parent, and
25% (1 in 4) chance to be unaffected and not be a carrier.

Autosomal dominant A pathogenic variant in only one gene copy in each cell is sufficient to cause an autosomal dominant disease.

Autosomal recessive Pathogenic variants in both copies of each gene of the chromosome are needed to cause an autosomal recessive disease and observe the mutant phenotype.

X-linked
dominant X-linked dominant inheritance, sometimes referred to as X-linked dominance, is a mode of genetic inheritance by which a dominant gene is carried on the X chromosome.

X-linked
recessive Pathogenic variants in both copies of a gene on the X chromosome cause an X-linked recessive disorder.

Mitochondrial or multigenic Mitochondrial genetic disorders can be caused by changes (mutations) in either the mitochondrial DNA or nuclear DNA that lead to dysfunction of the mitochondria and inadequate production of energy.

Multigenic or multifactor Inheritance involving many factors, of which at least one is genetic but none is of overwhelming importance, as in the causation of a disease by multiple genetic and environmental factors.

Not applicable

Other names (AKA)

Hypoplasminogenemia

Summary

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. The growths are caused by the deposition of fibrin (a protein involved in blood clotting) and by inflammation. The most common clinical finding is ligneous ('wood-like') conjunctivitis, a condition marked by redness and subsequent formation of pseudomembranes of part of the eye that progresses to white, yellow-white or red thick masses with a wood-like consistency that replace the normal mucosa. This can lead to vision loss. Growths in other areas can also lead to medical problems; those that occur in the gastrointestinal tract can cause ulcers, and growth in the windpipe can lead to breathing problems. Hydrocephalus may be present at birth in a small number of individuals.^[1]^[2] Type 1 plasminogen deficiency is caused by mutations in the PLG gene. It is inherited in an autosomal recessive pattern.^[2] Management depends upon the sites involved, but mainly focuses on managing the ligneous conjunctivitis.^[3]

Symptoms

Type 1 plasminogen deficiency is characterized by the formation of inflamed growths on the mucous membranes. The area of the body most commonly affected is the conjunctiva, which are the mucous membranes that protect the white part of the eye (the sclera) and line the eyelids. The most common symptom of this disorder is ligneous conjunctivitis. This occurs when a buildup of a protein called fibrin causes inflammation of the conjunctiva (conjunctivitis), leading to thick, woody (ligneous), inflamed growths. The growths usually appear yellow, white, or red in color. Ligneous conjunctivitis most often occurs on the inside of the eyelids. These growths can lead to tearing of the cornea, scarring, and vision loss.

Other, less commonly affected areas include the inside of the mouth and gums, ears, upper and lower gastrointestinal tract, lungs, and female reproductive tract. The central nervous system (brain and spinal cord) and skin may also be affected.^[4]^[5]^[3]

This table lists symptoms that people with this disease may have. For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed. This information comes from a database called the Human Phenotype Ontology (HPO) . The HPO collects information on symptoms that have been described in medical resources. The HPO is updated regularly. Use the HPO ID to access more in-depth information about a symptom.

Medical Terms	Other Names	Learn More: HPO ID
80%-99% of people have these symptoms
Abnormality of vision	Abnormality of sight Vision issue [ more ]	0000504
Decreased level of plasminogen		0040228
30%-79% of people have these symptoms
Gingival overgrowth	Gum enlargement	0000212
Gingivitis	Inflamed gums Red and swollen gums [ more ]	0000230
5%-29% of people have these symptoms
Abnormal fallopian tube morphology		0011027
Abnormality of the middle ear		0000370
Abnormality of the ovary	Abnormality of the ovaries	0000137
Abnormality of the respiratory system		0002086
Abnormality of the skin		0000951
Cervicitis	Uterine cervix inflammation	0030160
Dandy-Walker malformation		0001305
Duodenal ulcer		0002588
Hydrocephalus	Too much cerebrospinal fluid in the brain	0000238
Nephritis	Kidney inflammation	0000123
Nephrolithiasis	Kidney stones	0000787
Periodontitis		0000704
Percent of people who have these symptoms is not available through HPO
Abnormality of metabolism/homeostasis	Laboratory abnormality Metabolism abnormality [ more ]	0001939
Abnormality of the ear		0000598
Abnormality of the larynx		0001600
Autosomal recessive inheritance		0000007
Blindness		0000618
Cerebellar hypoplasia	Small cerebellum Underdeveloped cerebellum [ more ]	0001321
Conjunctivitis	Pink eye	0000509
Infantile onset	Onset in first year of life Onset in infancy [ more ]	0003593
Macrocephaly	Increased size of skull Large head Large head circumference [ more ]	0000256
Recurrent upper respiratory tract infections	Recurrent colds	0002788

Do you have updated information on this disease? We want to hear from you.

Cause

Type 1 plasminogen deficiency is caused by mutations in the PLG gene. This gene provides instructions for making a protein called plasminogen.^[2]^[3] Enzymes called plasminogen activators convert plasminogen into the protein plasmin, whose function is to dissolve fibrin clots. Fibrin clots form scabs at a wound site, providing the framework for new tissue growth.^[2] PLG mutations can decrease the amount of plasminogen that is produced, alter its function, or both. When the mutations affect plasminogen levels as well as the activity of the protein, type 1 plasminogen deficiency results.^[2]^[3] A reduction in functional plasminogen results in less plasmin, which allows fibrin to buildup. The excess fibrin and the resulting inflammation of the tissue result in the inflamed woody growth characteristic of this condition.^[2]

Diagnosis

Making a diagnosis for a genetic or rare disease can often be challenging. Healthcare professionals typically look at a person’s medical history, symptoms, physical exam, and laboratory test results in order to make a diagnosis. The following resources provide information relating to diagnosis and testing for this condition. If you have questions about getting a diagnosis, you should contact a healthcare professional.

Testing Resources

Orphanet lists international laboratories offering diagnostic testing for this condition.

Treatment

There is currently no established approach to treatment of type 1 plasminogen deficiency.^[6] 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.^[7]^[8] Clinical trials regarding the use of plasminogen replacement therapy are ongoing.^[9]

Learn more

These resources provide more information about this condition or associated symptoms. The in-depth resources contain medical and scientific language that may be hard to understand. You may want to review these resources with a medical professional.

Where to Start

Genetics Home Reference (GHR) contains information on Type 1 plasminogen deficiency. This website is maintained by the National Library of Medicine.
The National Organization for Rare Disorders (NORD) has a report for patients and families about this condition. NORD is a patient advocacy organization for individuals with rare diseases and the organizations that serve them.

In-Depth Information

The Monarch Initiative brings together data about this condition from humans and other species to help physicians and biomedical researchers. Monarch’s tools are designed to make it easier to compare the signs and symptoms (phenotypes) of different diseases and discover common features. This initiative is a collaboration between several academic institutions across the world and is funded by the National Institutes of Health. Visit the website to explore the biology of this condition.
Online Mendelian Inheritance in Man (OMIM) is a catalog of human genes and genetic disorders. Each entry has a summary of related medical articles. It is meant for health care professionals and researchers. OMIM is maintained by Johns Hopkins University School of Medicine.
Orphanet is a European reference portal for information on rare diseases and orphan drugs. Access to this database is free of charge.
PubMed is a searchable database of medical literature and lists journal articles that discuss Type 1 plasminogen deficiency. Click on the link to view a sample search on this topic.

References

Ginsburg D. Hemophilia and Other Disorders of Hemostasis. In: Rimoin DL, Connor JM, Pyeritz RE, Korf BR. Emery and Rimoin's Principles and Practice of Medical Genetics, 5th ed. Philadelphia: Elsevier Ltd; 2007;
Congenital plaminogen deficiency. Genetics Home Reference (GHR). August 2012; https://ghr.nlm.nih.gov/condition/congenital-plasminogen-deficiency.
Schuster V. Hypoplasminogenemia. Orphanet. May 2008; https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=en&Expert=722.
Tefs K, Gueorguieva M, Klammt J, Allen CM, Aktas D, Anlar FY et al. Molecular and clinical spectrum of type I plasminogen deficiency: a series of 50 patients. Blood. November 2006; https://www.ncbi.nlm.nih.gov/pubmed/16849641.
Congenital plasminogen deficiency. Genetics Home Reference (GHR). August 2012; https://ghr.nlm.nih.gov/condition/congenital-plasminogen-deficiency. Accessed 4/29/2013.
Celkan T. Plasminogen deficiency. J Thromb Thrombolysis. January, 2017; 43(1):132-138.
Colman RW, Marder VJ, Clowes AW, George JN, Goldhaber SZ. Hemostasis and Thrombosis. Philadelphia: Lippincott Williams & Wilkins; 2005;
Michael J. Ang, Konstantinos I. Papageorgiou, Shu-Hong Chang, Jocelyn Kohn, Helen Chokron Garneau, Robert A. Goldberg. Topical Plasminogen as Adjunctive Treatment in Recurrent Ligneous Conjunctivitis. Ophthal Plast Reconstr Surg. April 8, 2016; https://www.ncbi.nlm.nih.gov/pubmed/27065432.
Fay WP. Thrombotic and hemorrhagic disorders due to abnormal fibrinolysis. UpToDate. Waltham, MA: UpToDate; August, 2015;

Rare Dermatology News

Rare Dermatology News

Rare Dermatology News

All ages

L90.5

Autosomal dominant A pathogenic variant in only one gene copy in each cell is sufficient to cause an autosomal dominant disease.

Autosomal recessive Pathogenic variants in both copies of each gene of the chromosome are needed to cause an autosomal recessive disease and observe the mutant phenotype.

X-linked dominant X-linked dominant inheritance, sometimes referred to as X-linked dominance, is a mode of genetic inheritance by which a dominant gene is carried on the X chromosome.

X-linked recessive Pathogenic variants in both copies of a gene on the X chromosome cause an X-linked recessive disorder.

Mitochondrial or multigenic Mitochondrial genetic disorders can be caused by changes (mutations) in either the mitochondrial DNA or nuclear DNA that lead to dysfunction of the mitochondria and inadequate production of energy.

Multigenic or multifactor Inheritance involving many factors, of which at least one is genetic but none is of overwhelming importance, as in the causation of a disease by multiple genetic and environmental factors.

Not applicable

Other names (AKA)

Categories

Summary

Symptoms

Cause

Diagnosis

Testing Resources

Treatment

Learn more

Where to Start

In-Depth Information

References

X-linked
dominant X-linked dominant inheritance, sometimes referred to as X-linked dominance, is a mode of genetic inheritance by which a dominant gene is carried on the X chromosome.

X-linked
recessive Pathogenic variants in both copies of a gene on the X chromosome cause an X-linked recessive disorder.