Amol Sura, MD, Foster Center for Ocular Immunology, Dept of Ophthalmology, Duke University, Durham, North Carolina, discusses the diagnosis and management of plasminogen deficiency, a rare condition in which the eyes are first affected, but it manifests in mucous membranes throughout the body.

“The eyes are a window into the health of the entire body,” said Dr. Sura, and that is precisely the case for patients with plasminogen deficiency type 1 (PLGD-1). For this rare, inherited condition, the first symptom observed is the growth of ligneous or wood-like lesions on the surface of the eye or eyelid (in about 80% of patients, first seen at ages 9–10 months). It is often characterized as ligneous conjunctivitis. 

If left untreated, PLGD-1 may result in severe—even life-threatening—complications, affecting mucous membranes in many other areas of the body, including the respiratory tract, central nervous system, gingiva, and genitourinary tract. Vision loss, tooth loss, and other serious outcomes have been reported. 

In this homozygous condition involving the PLG gene, the plasminogen protein is defective; it cannot effectively perform its intended function of breaking down fibrin. The result is the formation of fibrin clots appearing as ligneous growths or pseudomembranes. Once removed, these lesions reappear, and this should tip off the physician (most often an ophthalmologist) that something systemic is the cause.
The diagnosis of PLGD-1 is straightforward: A blood test showing decreased plasminogen activity levels is confirmatory. A genetic test is not necessary. 

In the past, management of PLGD-1 was through the use of off-label therapies, including heparin eyedrops, immunologics, and plasma infusions. A form of intravenous human plasminogen was approved by the U.S. Food and Drug Administration in 2021, and this is considered the standard of care today. With this therapy, plasminogen plasma levels can be restored, lowering the risk of new fibrin clots throughout the body. 

For newly diagnosed patients, the best advice for caregivers is to establish a relationship with a hematologist, who will serve as the principal care provider. Although a multidisciplinary care team is required (e.g., ophthalmology, obstetrics/gynecology, dentistry), the need for other specific providers will depend on the other organs or sites affected. 

Dr. Sura believes that PLDG-1 is underdiagnosed, but with increasing awareness, and the availability of effective treatment, diagnosis and management of these patients can be improved today.
For more information on PLGD-1, visit https://checkrare.com/plasminogen-deficiency-fibrin-accumulation-and-its-effects-on-patients-2/

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Geraldine Bliss, Co-Founder and President of CureSHANK, and Jenny Graham Beeson, Board Member for CureSHANK, discuss research in Phelan-McDermid syndrome (PMS) and the Start Genetic initiative.

PMS is a chromosome disorder caused by deletions at 22q13.3. The loss or the variation of the SHANK3 gene is likely responsible for many of the common features associated with PMS. Common symptoms include hypotonia, intellectual disability, developmental delays, and epilepsy. Differences in physical features may include long eyelashes, down slanting eyes, large ears, ears without normal folding, bulb-like tip of nose, pointed chin, large hands, and toenails that flake off as infants and then become hard and brittle as age. Unusual behaviors may include mouthing or chewing on non-food items, decreased perception of pain, and autistic-like behaviors such as flapping of hands and repetitive motions.

CureSHANK is a non-profit organization focused on finding a cure for PMS. It is currently involved in a variety of research studies focused on the development of novel therapies for PMS and getting them into clinical trials. Through collaboration with Neuren, the first patient was dosed in February 2026 in a phase 3 clinical trial of IGF-1 analog, NNZ-2591. As Ms. Bliss highlights, this marks the organization’s first phase 3 trial for PMS, helping to establish regulatory pathways for future treatments. Additionally, Jaguar Gene Therapy’s SHANK3 minigene replacement therapy has been officially dosed in five patients with no serious adverse events related to the therapy and early signs of improvement. The next step is a dose escalation study (NCT06662188).

CureSHANK is also working to facilitate natural history studies and the development of new biomarkers. Ms. Bliss explains this area of unmet need is caused by the diverse behavioral phenotypes of PMS that pose challenges in establishing outcome measures due to their subjectivity of improvement.

Genetic testing is also an area of focus for the organization, with their board members coming together to form Start Genetic. This initiative spreads awareness of genetic testing for a variety of genetic disorders through a Genetic Testing Action Day of July 25.

CHAPTERS
Introduction 00:00
PMS Overview 2:29
Current Management 5:09
Clinical Research 7:47
Next Steps 10:50
Genetic Testing 12:30
Take Home Message 14:52

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Amy Shapiro, MD, a pediatric hematologist and the Medical Director and CEO of the Indiana Hemophilia and Thrombosis Center in Indianapolis, provides CheckRare an overview on type 1 plasminogen deficiency (PLGD-1).

Plasminogen is a key enzyme that lyses fibrin throughout the body. When the body’s production of plasminogen is significantly impaired, the accumulation of fibrin causes ligneous growths in the eyes, airways, gastrointestinal tract, and in virtually any mucous membranous tissue.

The very rare, inherited genetic disorder PLGD-1 or plasminogen deficiency type 1, is characterized by the body’s inability to produce adequate quantities of plasminogen. Caused by a defect in the PLG gene, if one person is diagnosed, the other family members should be evaluated for this disorder as well.

If left untreated, PLGD-1 may result in severe complications, including vision loss/blindness, tooth loss with associated bone degradation, hearing impairment/loss, airway obstruction, and infertility. Furthermore, this disorder can present at birth with an immediate and severe manifestation—obstruction of the spinal fluid outflow tract, causing hydrocephalus (pressure build-up in the brain). Interestingly, Dr. Shapiro pointed out, patients with PLGD-1 do not experience excessive blood clotting, which might be expected in those unable to break up fibrin clots.

Most commonly, patients present in childhood (within 1 yr of age) with eye lesions, which can obscure the eye, irritate the cornea, and can cause vision loss. These lesions are often misdiagnosed as conjunctivitis. If the problem is resistant to treatment or if the ligneous growth, once removed, grows back, that is a key sign that PLDG-1 is the cause.

In patients with PLGD-1, the presentation can be quite variable, according to Dr. Shapiro, who has seen people with PLGD-1 who don’t present with symptoms until adulthood. As a result, diagnosis may take years because of an unusual presentation, and prognosis may be difficult to predict. At a prevalence of approximately 1.6 cases per 1 million population, most physicians are unfamiliar with PLGD-1.

Before 2021, management of these patients was focused on resolving each symptom or lesion. Patients who manifested hydrocephalus were given shunts to drain excess fluid, but these often became obstructed without adequate treatment. Systemic treatment was based on the infusion of fresh frozen plasma, which has low concentrations of plasminogen (thus requiring frequent infusions).

In 2021, a plasminogen concentrate, from human blood, was approved by the U.S. Food and Drug Administration. It rapidly increases plasminogen in blood. Today, many patients can be treated with home administration. Importantly, this agent treats all of the manifestations of PLGD-1 throughout the body.

The Plasminogen Deficiency Foundation is a valuable organization comprising people with affected family members or are patients themselves. It helps patients and care providers with disease education and support groups where they share experiences and network with others affected by this disorder.

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Amy Shapiro, MD, a pediatric hematologist and the Medical Director and CEO of the Indiana Hemophilia and Thrombosis Center in Indianapolis, provides CheckRare an overview on type 1 plasminogen deficiency (PLGD-1).

Plasminogen is a key enzyme that lyses fibrin throughout the body. When the body’s production of plasminogen is significantly impaired, the accumulation of fibrin causes ligneous growths in the eyes, airways, gastrointestinal tract, and in virtually any mucous membranous tissue.

The very rare, inherited genetic disorder PLGD-1 or plasminogen deficiency type 1, is characterized by the body’s inability to produce adequate quantities of plasminogen. Caused by a defect in the PLG gene, if one person is diagnosed, the other family members should be evaluated for this disorder as well.

If left untreated, PLGD-1 may result in severe complications, including vision loss/blindness, tooth loss with associated bone degradation, hearing impairment/loss, airway obstruction, and infertility. Furthermore, this disorder can present at birth with an immediate and severe manifestation—obstruction of the spinal fluid outflow tract, causing hydrocephalus (pressure build-up in the brain). Interestingly, Dr. Shapiro pointed out, patients with PLGD-1 do not experience excessive blood clotting, which might be expected in those unable to break up fibrin clots.

Most commonly, patients present in childhood (within 1 yr of age) with eye lesions, which can obscure the eye, irritate the cornea, and can cause vision loss. These lesions are often misdiagnosed as conjunctivitis. If the problem is resistant to treatment or if the ligneous growth, once removed, grows back, that is a key sign that PLDG-1 is the cause.

In patients with PLGD-1, the presentation can be quite variable, according to Dr. Shapiro, who has seen people with PLGD-1 who don’t present with symptoms until adulthood. As a result, diagnosis may take years because of an unusual presentation, and prognosis may be difficult to predict. At a prevalence of approximately 1.6 cases per 1 million population, most physicians are unfamiliar with PLGD-1.

Before 2021, management of these patients was focused on resolving each symptom or lesion. Patients who manifested hydrocephalus were given shunts to drain excess fluid, but these often became obstructed without adequate treatment. Systemic treatment was based on the infusion of fresh frozen plasma, which has low concentrations of plasminogen (thus requiring frequent infusions).

In 2021, a plasminogen concentrate, from human blood, was approved by the U.S. Food and Drug Administration. It rapidly increases plasminogen in blood. Today, many patients can be treated with home administration. Importantly, this agent treats all of the manifestations of PLGD-1 throughout the body.

The Plasminogen Deficiency Foundation is a valuable organization comprising people with affected family members or are patients themselves. It helps patients and care providers with disease education and support groups where they share experiences and network with others affected by this disorder.

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Amy Shapiro, MD, a pediatric hematologist and the Medical Director and CEO of the Indiana Hemophilia and Thrombosis Center in Indianapolis, provides CheckRare an overview on type 1 plasminogen deficiency (PLGD-1).

Plasminogen is a key enzyme that lyses fibrin throughout the body. When the body’s production of plasminogen is significantly impaired, the accumulation of fibrin causes ligneous growths in the eyes, airways, gastrointestinal tract, and in virtually any mucous membranous tissue.

The very rare, inherited genetic disorder PLGD-1 or plasminogen deficiency type 1, is characterized by the body’s inability to produce adequate quantities of plasminogen. Caused by a defect in the PLG gene, if one person is diagnosed, the other family members should be evaluated for this disorder as well.

If left untreated, PLGD-1 may result in severe complications, including vision loss/blindness, tooth loss with associated bone degradation, hearing impairment/loss, airway obstruction, and infertility. Furthermore, this disorder can present at birth with an immediate and severe manifestation—obstruction of the spinal fluid outflow tract, causing hydrocephalus (pressure build-up in the brain). Interestingly, Dr. Shapiro pointed out, patients with PLGD-1 do not experience excessive blood clotting, which might be expected in those unable to break up fibrin clots.

Most commonly, patients present in childhood (within 1 yr of age) with eye lesions, which can obscure the eye, irritate the cornea, and can cause vision loss. These lesions are often misdiagnosed as conjunctivitis. If the problem is resistant to treatment or if the ligneous growth, once removed, grows back, that is a key sign that PLDG-1 is the cause.

In patients with PLGD-1, the presentation can be quite variable, according to Dr. Shapiro, who has seen people with PLGD-1 who don’t present with symptoms until adulthood. As a result, diagnosis may take years because of an unusual presentation, and prognosis may be difficult to predict. At a prevalence of approximately 1.6 cases per 1 million population, most physicians are unfamiliar with PLGD-1.

Before 2021, management of these patients was focused on resolving each symptom or lesion. Patients who manifested hydrocephalus were given shunts to drain excess fluid, but these often became obstructed without adequate treatment. Systemic treatment was based on the infusion of fresh frozen plasma, which has low concentrations of plasminogen (thus requiring frequent infusions).

In 2021, a plasminogen concentrate, from human blood, was approved by the U.S. Food and Drug Administration. It rapidly increases plasminogen in blood. Today, many patients can be treated with home administration. Importantly, this agent treats all of the manifestations of PLGD-1 throughout the body.

The Plasminogen Deficiency Foundation is a valuable organization comprising people with affected family members or are patients themselves. It helps patients and care providers with disease education and support groups where they share experiences and network with others affected by this disorder.

0 0

Amy Shapiro, MD, a pediatric hematologist and the Medical Director and CEO of the Indiana Hemophilia and Thrombosis Center in Indianapolis, provides CheckRare an overview on type 1 plasminogen deficiency (PLGD-1).

Plasminogen is a key enzyme that lyses fibrin throughout the body. When the body’s production of plasminogen is significantly impaired, the accumulation of fibrin causes ligneous growths in the eyes, airways, gastrointestinal tract, and in virtually any mucous membranous tissue.

The very rare, inherited genetic disorder PLGD-1 or plasminogen deficiency type 1, is characterized by the body’s inability to produce adequate quantities of plasminogen. Caused by a defect in the PLG gene, if one person is diagnosed, the other family members should be evaluated for this disorder as well.

If left untreated, PLGD-1 may result in severe complications, including vision loss/blindness, tooth loss with associated bone degradation, hearing impairment/loss, airway obstruction, and infertility. Furthermore, this disorder can present at birth with an immediate and severe manifestation—obstruction of the spinal fluid outflow tract, causing hydrocephalus (pressure build-up in the brain). Interestingly, Dr. Shapiro pointed out, patients with PLGD-1 do not experience excessive blood clotting, which might be expected in those unable to break up fibrin clots.

Most commonly, patients present in childhood (within 1 yr of age) with eye lesions, which can obscure the eye, irritate the cornea, and can cause vision loss. These lesions are often misdiagnosed as conjunctivitis. If the problem is resistant to treatment or if the ligneous growth, once removed, grows back, that is a key sign that PLDG-1 is the cause.

In patients with PLGD-1, the presentation can be quite variable, according to Dr. Shapiro, who has seen people with PLGD-1 who don’t present with symptoms until adulthood. As a result, diagnosis may take years because of an unusual presentation, and prognosis may be difficult to predict. At a prevalence of approximately 1.6 cases per 1 million population, most physicians are unfamiliar with PLGD-1.

Before 2021, management of these patients was focused on resolving each symptom or lesion. Patients who manifested hydrocephalus were given shunts to drain excess fluid, but these often became obstructed without adequate treatment. Systemic treatment was based on the infusion of fresh frozen plasma, which has low concentrations of plasminogen (thus requiring frequent infusions).

In 2021, a plasminogen concentrate, from human blood, was approved by the U.S. Food and Drug Administration. It rapidly increases plasminogen in blood. Today, many patients can be treated with home administration. Importantly, this agent treats all of the manifestations of PLGD-1 throughout the body.

The Plasminogen Deficiency Foundation is a valuable organization comprising people with affected family members or are patients themselves. It helps patients and care providers with disease education and support groups where they share experiences and network with others affected by this disorder.

0 0

Amy Shapiro, MD, a pediatric hematologist and the Medical Director and CEO of the Indiana Hemophilia and Thrombosis Center in Indianapolis, provides CheckRare an overview on type 1 plasminogen deficiency (PLGD-1).

Plasminogen is a key enzyme that lyses fibrin throughout the body. When the body’s production of plasminogen is significantly impaired, the accumulation of fibrin causes ligneous growths in the eyes, airways, gastrointestinal tract, and in virtually any mucous membranous tissue.

The very rare, inherited genetic disorder PLGD-1 or plasminogen deficiency type 1, is characterized by the body’s inability to produce adequate quantities of plasminogen. Caused by a defect in the PLG gene, if one person is diagnosed, the other family members should be evaluated for this disorder as well.

If left untreated, PLGD-1 may result in severe complications, including vision loss/blindness, tooth loss with associated bone degradation, hearing impairment/loss, airway obstruction, and infertility. Furthermore, this disorder can present at birth with an immediate and severe manifestation—obstruction of the spinal fluid outflow tract, causing hydrocephalus (pressure build-up in the brain). Interestingly, Dr. Shapiro pointed out, patients with PLGD-1 do not experience excessive blood clotting, which might be expected in those unable to break up fibrin clots.

Most commonly, patients present in childhood (within 1 yr of age) with eye lesions, which can obscure the eye, irritate the cornea, and can cause vision loss. These lesions are often misdiagnosed as conjunctivitis. If the problem is resistant to treatment or if the ligneous growth, once removed, grows back, that is a key sign that PLDG-1 is the cause.

In patients with PLGD-1, the presentation can be quite variable, according to Dr. Shapiro, who has seen people with PLGD-1 who don’t present with symptoms until adulthood. As a result, diagnosis may take years because of an unusual presentation, and prognosis may be difficult to predict. At a prevalence of approximately 1.6 cases per 1 million population, most physicians are unfamiliar with PLGD-1.

Before 2021, management of these patients was focused on resolving each symptom or lesion. Patients who manifested hydrocephalus were given shunts to drain excess fluid, but these often became obstructed without adequate treatment. Systemic treatment was based on the infusion of fresh frozen plasma, which has low concentrations of plasminogen (thus requiring frequent infusions).

In 2021, a plasminogen concentrate, from human blood, was approved by the U.S. Food and Drug Administration. It rapidly increases plasminogen in blood. Today, many patients can be treated with home administration. Importantly, this agent treats all of the manifestations of PLGD-1 throughout the body.

The Plasminogen Deficiency Foundation is a valuable organization comprising people with affected family members or are patients themselves. It helps patients and care providers with disease education and support groups where they share experiences and network with others affected by this disorder.

0 0

Amy Shapiro, MD, a pediatric hematologist and the Medical Director and CEO of the Indiana Hemophilia and Thrombosis Center in Indianapolis, provides CheckRare an overview on type 1 plasminogen deficiency (PLGD-1).

Plasminogen is a key enzyme that lyses fibrin throughout the body. When the body’s production of plasminogen is significantly impaired, the accumulation of fibrin causes ligneous growths in the eyes, airways, gastrointestinal tract, and in virtually any mucous membranous tissue.

The very rare, inherited genetic disorder PLGD-1 or plasminogen deficiency type 1, is characterized by the body’s inability to produce adequate quantities of plasminogen. Caused by a defect in the PLG gene, if one person is diagnosed, the other family members should be evaluated for this disorder as well.

If left untreated, PLGD-1 may result in severe complications, including vision loss/blindness, tooth loss with associated bone degradation, hearing impairment/loss, airway obstruction, and infertility. Furthermore, this disorder can present at birth with an immediate and severe manifestation—obstruction of the spinal fluid outflow tract, causing hydrocephalus (pressure build-up in the brain). Interestingly, Dr. Shapiro pointed out, patients with PLGD-1 do not experience excessive blood clotting, which might be expected in those unable to break up fibrin clots.

Most commonly, patients present in childhood (within 1 yr of age) with eye lesions, which can obscure the eye, irritate the cornea, and can cause vision loss. These lesions are often misdiagnosed as conjunctivitis. If the problem is resistant to treatment or if the ligneous growth, once removed, grows back, that is a key sign that PLDG-1 is the cause.

In patients with PLGD-1, the presentation can be quite variable, according to Dr. Shapiro, who has seen people with PLGD-1 who don’t present with symptoms until adulthood. As a result, diagnosis may take years because of an unusual presentation, and prognosis may be difficult to predict. At a prevalence of approximately 1.6 cases per 1 million population, most physicians are unfamiliar with PLGD-1.

Before 2021, management of these patients was focused on resolving each symptom or lesion. Patients who manifested hydrocephalus were given shunts to drain excess fluid, but these often became obstructed without adequate treatment. Systemic treatment was based on the infusion of fresh frozen plasma, which has low concentrations of plasminogen (thus requiring frequent infusions).

In 2021, a plasminogen concentrate, from human blood, was approved by the U.S. Food and Drug Administration. It rapidly increases plasminogen in blood. Today, many patients can be treated with home administration. Importantly, this agent treats all of the manifestations of PLGD-1 throughout the body.

The Plasminogen Deficiency Foundation is a valuable organization comprising people with affected family members or are patients themselves. It helps patients and care providers with disease education and support groups where they share experiences and network with others affected by this disorder.

0 0

Amy Shapiro, MD, a pediatric hematologist and the Medical Director and CEO of the Indiana Hemophilia and Thrombosis Center in Indianapolis, provides CheckRare an overview on type 1 plasminogen deficiency (PLGD-1).

Plasminogen is a key enzyme that lyses fibrin throughout the body. When the body’s production of plasminogen is significantly impaired, the accumulation of fibrin causes ligneous growths in the eyes, airways, gastrointestinal tract, and in virtually any mucous membranous tissue.

The very rare, inherited genetic disorder PLGD-1 or plasminogen deficiency type 1, is characterized by the body’s inability to produce adequate quantities of plasminogen. Caused by a defect in the PLG gene, if one person is diagnosed, the other family members should be evaluated for this disorder as well.

If left untreated, PLGD-1 may result in severe complications, including vision loss/blindness, tooth loss with associated bone degradation, hearing impairment/loss, airway obstruction, and infertility. Furthermore, this disorder can present at birth with an immediate and severe manifestation—obstruction of the spinal fluid outflow tract, causing hydrocephalus (pressure build-up in the brain). Interestingly, Dr. Shapiro pointed out, patients with PLGD-1 do not experience excessive blood clotting, which might be expected in those unable to break up fibrin clots.

Most commonly, patients present in childhood (within 1 yr of age) with eye lesions, which can obscure the eye, irritate the cornea, and can cause vision loss. These lesions are often misdiagnosed as conjunctivitis. If the problem is resistant to treatment or if the ligneous growth, once removed, grows back, that is a key sign that PLDG-1 is the cause.

In patients with PLGD-1, the presentation can be quite variable, according to Dr. Shapiro, who has seen people with PLGD-1 who don’t present with symptoms until adulthood. As a result, diagnosis may take years because of an unusual presentation, and prognosis may be difficult to predict. At a prevalence of approximately 1.6 cases per 1 million population, most physicians are unfamiliar with PLGD-1.

Before 2021, management of these patients was focused on resolving each symptom or lesion. Patients who manifested hydrocephalus were given shunts to drain excess fluid, but these often became obstructed without adequate treatment. Systemic treatment was based on the infusion of fresh frozen plasma, which has low concentrations of plasminogen (thus requiring frequent infusions).

In 2021, a plasminogen concentrate, from human blood, was approved by the U.S. Food and Drug Administration. It rapidly increases plasminogen in blood. Today, many patients can be treated with home administration. Importantly, this agent treats all of the manifestations of PLGD-1 throughout the body.

The Plasminogen Deficiency Foundation is a valuable organization comprising people with affected family members or are patients themselves. It helps patients and care providers with disease education and support groups where they share experiences and network with others affected by this disorder.

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