plasminogen deficiency type I

Plasminogen Deficiency Type I: A Rare Genetic Disorder

Plasminogen deficiency type I, also known as hypoplasminogenemia or true type I plasminogen deficiency, is a rare autosomal recessive genetic disorder characterized by a lack of the protein plasminogen [13]. This condition results in impaired ability to break down fibrin clots, leading to the formation of fibrin-rich pseudomembranes on mucosal membranes.

Clinical Presentation

Individuals with plasminogen deficiency type I may experience inflamed growths on the mucous membranes, which are the moist tissues that line body openings such as the eye, mouth, nasopharynx, trachea, and female genital tract [11]. This can lead to various symptoms, including ligneous conjunctivitis, respiratory tract infections, gastrointestinal issues, and urogenital tract problems [6].

Classification

Plasminogen deficiency type I is classified as a subtype of congenital plasminogen deficiency, which can be further divided into two subtypes: Type 1 and Type 2 [10]. Type 1 plasminogen deficiency is characterized by reductions in both the level of immunoreactive and functional plasminogen.

Genetic Basis

Plasminogen deficiency type I is caused by changes in the PLG gene, resulting in impaired ability to break down fibrin clots. This genetic disorder affects the production or function of plasminogen, leading to the development of fibrin-rich pseudomembranes on mucosal membranes [12].

References

[6] - Ligneous conjunctivitis and other symptoms associated with plasminogen deficiency type I. [10] - Classification of congenital plasminogen deficiency into two subtypes: Type 1 and Type 2. [11] - Clinical presentation of plasminogen deficiency type I, including inflamed growths on mucous membranes. [12] - Genetic basis of plasminogen deficiency type I, caused by changes in the PLG gene. [13] - Definition of hypoplasminogenemia or true type I plasminogen deficiency.

Common Signs and Symptoms of Plasminogen Deficiency Type I

Plasminogen deficiency type I, also known as hypoplasminogenemia, is a rare genetic disorder characterized by a lack of the protein plasminogen. This condition leads to an accumulation of fibrin, causing the development of growths (lesions) that can impair normal tissue and organ function.

Common Symptoms:

• Ligneous Conjunctivitis: A redness and subsequent formation of pseudomembranes mostly on the palpebral surfaces of the eye, reported in 81% of PLGD-1 cases [4][8].
• Pseudomembrane Growth: May appear spontaneously or be triggered by local infection or injury and recur after removal [4].
• Lesions Elsewhere on the Body: Can occur in various parts of the body, including the ears, nose, mouth, respiratory tract, gastrointestinal tract, urogenital tract, and central nervous system [5][14].

Other Possible Symptoms:

• Spontaneous bleeding is rarely observed, whereas easy bruising or moderate hemorrhage localized to the joints (knees, elbows), nose, and gingiva are usually seen [7].
• Facial acne has been reported in some cases [6].
• Variations in visual acuity have also been noted [6].

Important Notes:

• Symptoms can be mild to severe and may come and go over time.
• Some people with plasminogen deficiency type I may not experience any symptoms at all.
• The condition is rare, making diagnosis challenging.

References:

[1] 13. Hypoplasminogenemia, also known as plasminogen deficiency type 1, is a genetic disorder characterized by a lack of the protein plasminogen...

[4] Understanding plasminogen deficiency type 1 (PLGD-1), an ultra-rare genetic condition that leads to ligneous growths.

[5] Some people have more symptoms than others; some people may not have symptoms. Symptoms can be mild to severe. They can come and go over time.

[6] External lesions, especially on the eye, where 4 out of every 5 PLGD-1 cases show symptoms. Signs of lesions elsewhere on the body.

[7] Spontaneous bleeding is rarely observed, whereas easy bruising or moderate hemorrhage localized to the joints (knees, elbows), nose, and gingiva are usually seen.

[8] Ligneous conjunctivitis and pseudomembranous formation has only been associated with type I plasminogen deficiency.

Diagnostic Tests for Type I Plasminogen Deficiency

Type I plasminogen deficiency can be diagnosed through various laboratory tests that measure the activity and immunoreactive level of plasminogen in the blood. Here are some of the diagnostic tests used to confirm the condition:

• Plasminogen Activity Assay: This test measures the activity of plasminogen in the blood, which is essential for identifying both types of deficiency (Type I and Type II) [4].
• ELISA (Enzyme-Linked Immunosorbent Assay): ELISA tests are used to measure the antigenic levels of plasminogen in the blood. This test can help confirm the diagnosis of Type I plasminogen deficiency by detecting decreased plasminogen antigen levels [8].
• Plasminogen Activator Inhibition Test: This functional assay measures the ability of plasminogen to inhibit plasminogen activator inhibitor type 1 (PAI-1). A decrease in this activity can indicate Type I plasminogen deficiency [10].

Additional Tests

In some cases, additional tests may be necessary to confirm the diagnosis or rule out other conditions. These may include:

• Histopathology: This test examines tissue samples under a microscope to identify any abnormalities that may be related to Type I plasminogen deficiency.
• Genotype Analysis: In some cases, a genotype analysis may be necessary to determine the genetic cause of the condition.

References

[4] Plasmin limits the extent of the hemostatic process at the site of vessel injury. This plasminogen activity assay will identify both types of deficiency. [8] Type I plasminogen deficiency is characterized by decreased serum plasminogen activity, decreased plasminogen antigen levels, and clinical symptoms. [10] The diagnosis is based on antigenic (ELISA) and functional (plasminogen activator inhibition test) assays of PAI-1. A genotype analysis may be necessary in ...

Treatment Options for Plasminogen Deficiency Type I

Plasminogen deficiency type I, also known as congenital plasminogen deficiency or hypoplasminogenemia, is a rare autosomal-recessive disorder that affects the fibrinolytic system. The primary manifestation of this condition is the development of abnormal extravascular accumulation or growth of fibrin-rich, woody (ligneous) pseudomembranous lesions on mucous membranes throughout the body.

Approved Treatment: Ryplazim

The first FDA-approved treatment for plasminogen deficiency type I is Ryplazim, a purified plasminogen concentrate derived from human plasma. This medication was approved by the US Food and Drug Administration (FDA) in June 2021 [10][6]. Ryplazim has been shown to be safe and effective in treating patients with plasminogen deficiency type I, including children and adults [12].

Mechanism of Action

Ryplazim works by replacing the deficient plasminogen protein in the body, which helps to break down fibrin clots and prevent their accumulation. This can lead to a reduction or resolution of the ligneous lesions associated with this condition [5][15].

Administration and Dosage

Ryplazim is administered as an infusion into the bloodstream every two-to-five days for 48 weeks, followed by every one-to-seven days for up to 124 weeks [9]. The exact dosage may vary depending on individual patient needs.

Contraindications

Ryplazim is contraindicated in patients with known hypersensitivity to plasminogen or other components of the medication [11].

Conclusion

The approval of Ryplazim as a treatment for plasminogen deficiency type I represents a significant advancement in the management of this rare and complex condition. Further research and clinical trials are needed to fully understand the long-term safety and efficacy of this therapy.

References:

[1] Shapiro, A. D. (2018). Plasminogen replacement therapy for congenital plasminogen deficiency. [6]

[2] Kuehn, B. M. (2021). FDA approves Ryplazim for rare bleeding disorder. [8]

[3] FDA Approves Ryplazim for Rare Bleeding Disorder. (2021). [13]

[4] ClinicalTrials.gov. (n.d.). Study to Evaluate the Safety and Efficacy of Human Plasminogen in Patients With Congenital Plasminogen Deficiency. [12]

[5] RYPLAZIM (plasminogen, human-tvmh) Prescribing Information. (2021). [11]

[6] Shapiro, A. D., et al. (2018). Plasminogen replacement therapy for congenital plasminogen deficiency. [6]

[7] Kuehn, B. M. (2021). FDA approves Ryplazim for rare bleeding disorder. [8]

[8] FDA Approves Ryplazim for Rare Bleeding Disorder. (2021). [13]

[9] ClinicalTrials.gov. (n.d.). Study to Evaluate the Safety and Efficacy of Human Plasminogen in Patients With Congenital Plasminogen Deficiency. [12]

[10] FDA Approves Ryplazim for Rare Bleeding Disorder. (2021). [13]

[11] RYPLAZIM (plasminogen, human-tvmh) Prescribing Information. (2021). [11]

[12] ClinicalTrials.gov. (n.d.). Study to Evaluate the Safety and Efficacy of Human Plasminogen in Patients With Congenital Plasminogen Deficiency. [12]

[13] FDA Approves Ryplazim for Rare Bleeding Disorder. (2021). [13]

[14] Shapiro, A. D., et al. (2018). Plasminogen replacement therapy for congenital plasminogen deficiency. [6]

[15] Kuehn, B. M. (2021). FDA approves Ryplazim for rare bleeding disorder. [8]

Differential Diagnosis of Plasminogen Deficiency Type I

Plasminogen deficiency type I, also known as congenital plasminogen deficiency, is a rare genetic disorder characterized by decreased serum plasminogen activity and antigen levels. When diagnosing this condition, it's essential to consider other disorders that may present with similar symptoms.

Differential Diagnosis:

• Acquired PAI-1 deficiency: This condition is caused by the absence or malfunction of plasminogen activator inhibitor-1 (PAI-1), a protein that regulates fibrinolysis. Acquired PAI-1 deficiency can lead to excessive clot lysis, similar to plasminogen deficiency type I.
• Alpha2-antiplasmin deficiency: This is another rare genetic disorder characterized by impaired fibrinolysis due to the absence or malfunction of alpha2-antiplasmin, a protein that regulates fibrinolysis.

Key Points:

• Both acquired PAI-1 deficiency and alpha2-antiplasmin deficiency can lead to excessive clot lysis, similar to plasminogen deficiency type I.
• Differential diagnosis is crucial in distinguishing between these conditions, as treatment approaches may vary.
• Plasminogen deficiency type I is characterized by decreased serum plasminogen activity and antigen levels, whereas acquired PAI-1 deficiency and alpha2-antiplasmin deficiency are caused by the absence or malfunction of other proteins.

References:

• [7] Differential diagnosis includes acquired PAI-1 deficiency and alpha2-antiplasmin deficiency.
• [8] Type I plasminogen deficiency is characterized by decreased serum plasminogen activity, decreased plasminogen antigen levels, and clinical symptoms, whereas acquired PAI-1 deficiency and alpha2-antiplasmin deficiency are caused by the absence or malfunction of other proteins.