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 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.

0 0

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 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.

CHAPTERS
Introduction 00:00
PLGD Overview 1:11
Diagnostic Pathway 2:23
Role of Genetic Testing 3:25
Serious Complications 4:00
Advice for Newly Diagnosed Patients 4:42
Take Home Message 6:07

0 0

Angela Zhu, MD, is an Ophthalmologist and Clinical Assistant Professor, Pediatric & Adult Cornea/Cataract/External Diseases, at Bascom Palmer Eye Institute in Miami. In this interview with
CheckRare, Dr. Zhu describes some of the key features of plasminogen deficiency and why ophthalmologists are often the healthcare providers who begin the process toward diagnosis.

Plasminogen deficiency type 1 (PLGD-1) is a rare genetic disorder in which the body fails to make adequate quantities of plasminogen, the molecule responsible for protection against abnormal fibrin clotting. It generally manifests initially (in about 80%) as ligneous conjunctivitis, in which thick membraneous lesions (from from fibrin accumulation) develop on the surface of the eye and in the eyelid. As a result, Dr. Zhu said, ophthalmologists are usually the first healthcare provider to see the patient and start the diagnostic journey.

Even though the ligneous lesions on the eye are generally the first symptom in young patients, PLGD-1 can present in many different ways (and in virtually any organ system with mucous membranes). However, fibrin accumulations in internal organs or tissue may be harder to detect.
The diagnosis may not be obvious, especially if the telltale ophthalmologic sign is misread as common infectious conjunctivitis. Patients with PLGD1 can have multiple other symptoms that wax and wane, said Dr. Zhu, and “we need to educate providers about the disease and how it can present. It is underdiagnosed and underrecognized.”

In patients with ligneous conjunctivitis, these fibrous lesions can first be mistaken for discharge, which is common in infectious conjunctivitis. But it doesn’t respond to treatment, unlike viral or bacterial causes of conjunctivitis would. Once the ligneous lesion is removed from the eye, because the plasminogen deficiency is not remedied, it will likely form again.

In the case of these eye lesions or conjunctivitis that doesn’t resolve with antiallergy, steroidal, or antiviral treatment, or grow back after removal, Dr. Zhu stated that laboratory testing for plasminogen activity and antigen testing should be the next step. It will diagnose the condition. “But it could take months before a provider makes the connection [that PLGD1 is the cause].”

The extravascular, fibrin-rich lesions that appear anywhere there is mucous membranes can cause serious or even life-threatening complications. For example, the growths could cause airway obstruction, renal failure if the kidney is involved, chronic hearing loss, or blindness.

“Prior to 2023, we didn’t have an FDA-approved treatment,” she noted. Fresh frozen plasma infusions, which had low plasminogen concentrations, were the mainstay. In 2023, the FDA approved a human-derived plasminogen infusion, which effectively raises plasminogen blood concentrations and ensures adequate plasminogen activity. Plasminogen infusions must be given every two to four days. Five years after initializing therapy, patients have remained free of new lesions, said Dr. Zhu.

The adverse events associated with the infusion include infusion-site reactions, bloating, nausea, and fatigue. She also related that there is a theoretical risk for introduction of infection (as it is a blood product). The fibrin-rich growths can suddenly slough off with therapy, and this could potentially cause unique problems (e.g., a sizeable lesion in the airway breaking off) or bleeding.

CHAPTERS
Introduction 00:00
Plasminogen Deficiency Type 1 Overview 00:56
Diagnostic Odyssey 2:36
Disease Complications 6:08

0 0

Angela Zhu, MD, is an Ophthalmologist and Clinical Assistant Professor, Pediatric & Adult Cornea/Cataract/External Diseases, at Bascom Palmer Eye Institute in Miami. In this interview with
CheckRare, Dr. Zhu describes some of the key features of plasminogen deficiency and why ophthalmologists are often the healthcare providers who begin the process toward diagnosis.

Plasminogen deficiency type 1 (PLGD-1) is a rare genetic disorder in which the body fails to make adequate quantities of plasminogen, the molecule responsible for protection against abnormal fibrin clotting. It generally manifests initially (in about 80%) as ligneous conjunctivitis, in which thick membraneous lesions (from from fibrin accumulation) develop on the surface of the eye and in the eyelid. As a result, Dr. Zhu said, ophthalmologists are usually the first healthcare provider to see the patient and start the diagnostic journey.

Even though the ligneous lesions on the eye are generally the first symptom in young patients, PLGD-1 can present in many different ways (and in virtually any organ system with mucous membranes). However, fibrin accumulations in internal organs or tissue may be harder to detect.
The diagnosis may not be obvious, especially if the telltale ophthalmologic sign is misread as common infectious conjunctivitis. Patients with PLGD1 can have multiple other symptoms that wax and wane, said Dr. Zhu, and “we need to educate providers about the disease and how it can present. It is underdiagnosed and underrecognized.”

In patients with ligneous conjunctivitis, these fibrous lesions can first be mistaken for discharge, which is common in infectious conjunctivitis. But it doesn’t respond to treatment, unlike viral or bacterial causes of conjunctivitis would. Once the ligneous lesion is removed from the eye, because the plasminogen deficiency is not remedied, it will likely form again.

In the case of these eye lesions or conjunctivitis that doesn’t resolve with antiallergy, steroidal, or antiviral treatment, or grow back after removal, Dr. Zhu stated that laboratory testing for plasminogen activity and antigen testing should be the next step. It will diagnose the condition. “But it could take months before a provider makes the connection [that PLGD1 is the cause].”

The extravascular, fibrin-rich lesions that appear anywhere there is mucous membranes can cause serious or even life-threatening complications. For example, the growths could cause airway obstruction, renal failure if the kidney is involved, chronic hearing loss, or blindness.

“Prior to 2023, we didn’t have an FDA-approved treatment,” she noted. Fresh frozen plasma infusions, which had low plasminogen concentrations, were the mainstay. In 2023, the FDA approved a human-derived plasminogen infusion, which effectively raises plasminogen blood concentrations and ensures adequate plasminogen activity. Plasminogen infusions must be given every two to four days. Five years after initializing therapy, patients have remained free of new lesions, said Dr. Zhu.

The adverse events associated with the infusion include infusion-site reactions, bloating, nausea, and fatigue. She also related that there is a theoretical risk for introduction of infection (as it is a blood product). The fibrin-rich growths can suddenly slough off with therapy, and this could potentially cause unique problems (e.g., a sizeable lesion in the airway breaking off) or bleeding.

0 0

Angela Zhu, MD, is an Ophthalmologist and Clinical Assistant Professor, Pediatric & Adult Cornea/Cataract/External Diseases, at Bascom Palmer Eye Institute in Miami. In this interview with
CheckRare, Dr. Zhu describes some of the key features of plasminogen deficiency and why ophthalmologists are often the healthcare providers who begin the process toward diagnosis.

Plasminogen deficiency type 1 (PLGD-1) is a rare genetic disorder in which the body fails to make adequate quantities of plasminogen, the molecule responsible for protection against abnormal fibrin clotting. It generally manifests initially (in about 80%) as ligneous conjunctivitis, in which thick membraneous lesions (from from fibrin accumulation) develop on the surface of the eye and in the eyelid. As a result, Dr. Zhu said, ophthalmologists are usually the first healthcare provider to see the patient and start the diagnostic journey.

Even though the ligneous lesions on the eye are generally the first symptom in young patients, PLGD-1 can present in many different ways (and in virtually any organ system with mucous membranes). However, fibrin accumulations in internal organs or tissue may be harder to detect.
The diagnosis may not be obvious, especially if the telltale ophthalmologic sign is misread as common infectious conjunctivitis. Patients with PLGD1 can have multiple other symptoms that wax and wane, said Dr. Zhu, and “we need to educate providers about the disease and how it can present. It is underdiagnosed and underrecognized.”

In patients with ligneous conjunctivitis, these fibrous lesions can first be mistaken for discharge, which is common in infectious conjunctivitis. But it doesn’t respond to treatment, unlike viral or bacterial causes of conjunctivitis would. Once the ligneous lesion is removed from the eye, because the plasminogen deficiency is not remedied, it will likely form again.

In the case of these eye lesions or conjunctivitis that doesn’t resolve with antiallergy, steroidal, or antiviral treatment, or grow back after removal, Dr. Zhu stated that laboratory testing for plasminogen activity and antigen testing should be the next step. It will diagnose the condition. “But it could take months before a provider makes the connection [that PLGD1 is the cause].”

The extravascular, fibrin-rich lesions that appear anywhere there is mucous membranes can cause serious or even life-threatening complications. For example, the growths could cause airway obstruction, renal failure if the kidney is involved, chronic hearing loss, or blindness.

“Prior to 2023, we didn’t have an FDA-approved treatment,” she noted. Fresh frozen plasma infusions, which had low plasminogen concentrations, were the mainstay. In 2023, the FDA approved a human-derived plasminogen infusion, which effectively raises plasminogen blood concentrations and ensures adequate plasminogen activity. Plasminogen infusions must be given every two to four days. Five years after initializing therapy, patients have remained free of new lesions, said Dr. Zhu.

The adverse events associated with the infusion include infusion-site reactions, bloating, nausea, and fatigue. She also related that there is a theoretical risk for introduction of infection (as it is a blood product). The fibrin-rich growths can suddenly slough off with therapy, and this could potentially cause unique problems (e.g., a sizeable lesion in the airway breaking off) or bleeding.

0 0

Angela Zhu, MD, is an Ophthalmologist and Clinical Assistant Professor, Pediatric & Adult Cornea/Cataract/External Diseases, at Bascom Palmer Eye Institute in Miami. In this interview with
CheckRare, Dr. Zhu describes some of the key features of plasminogen deficiency and why ophthalmologists are often the healthcare providers who begin the process toward diagnosis.

Plasminogen deficiency type 1 (PLGD-1) is a rare genetic disorder in which the body fails to make adequate quantities of plasminogen, the molecule responsible for protection against abnormal fibrin clotting. It generally manifests initially (in about 80%) as ligneous conjunctivitis, in which thick membraneous lesions (from from fibrin accumulation) develop on the surface of the eye and in the eyelid. As a result, Dr. Zhu said, ophthalmologists are usually the first healthcare provider to see the patient and start the diagnostic journey.

Even though the ligneous lesions on the eye are generally the first symptom in young patients, PLGD-1 can present in many different ways (and in virtually any organ system with mucous membranes). However, fibrin accumulations in internal organs or tissue may be harder to detect.
The diagnosis may not be obvious, especially if the telltale ophthalmologic sign is misread as common infectious conjunctivitis. Patients with PLGD1 can have multiple other symptoms that wax and wane, said Dr. Zhu, and “we need to educate providers about the disease and how it can present. It is underdiagnosed and underrecognized.”

In patients with ligneous conjunctivitis, these fibrous lesions can first be mistaken for discharge, which is common in infectious conjunctivitis. But it doesn’t respond to treatment, unlike viral or bacterial causes of conjunctivitis would. Once the ligneous lesion is removed from the eye, because the plasminogen deficiency is not remedied, it will likely form again.

In the case of these eye lesions or conjunctivitis that doesn’t resolve with antiallergy, steroidal, or antiviral treatment, or grow back after removal, Dr. Zhu stated that laboratory testing for plasminogen activity and antigen testing should be the next step. It will diagnose the condition. “But it could take months before a provider makes the connection [that PLGD1 is the cause].”

The extravascular, fibrin-rich lesions that appear anywhere there is mucous membranes can cause serious or even life-threatening complications. For example, the growths could cause airway obstruction, renal failure if the kidney is involved, chronic hearing loss, or blindness.

“Prior to 2023, we didn’t have an FDA-approved treatment,” she noted. Fresh frozen plasma infusions, which had low plasminogen concentrations, were the mainstay. In 2023, the FDA approved a human-derived plasminogen infusion, which effectively raises plasminogen blood concentrations and ensures adequate plasminogen activity. Plasminogen infusions must be given every two to four days. Five years after initializing therapy, patients have remained free of new lesions, said Dr. Zhu.

The adverse events associated with the infusion include infusion-site reactions, bloating, nausea, and fatigue. She also related that there is a theoretical risk for introduction of infection (as it is a blood product). The fibrin-rich growths can suddenly slough off with therapy, and this could potentially cause unique problems (e.g., a sizeable lesion in the airway breaking off) or bleeding.

0 0

Richard J. Auchus, MD, PhD, Professor of Internal Medicine and Pharmacology at the University of Michigan Medical School, discusses two-year results of Crenessity (crinecerfont) in the treatment of congenital adrenal hyperplasia (CAH).

CAH refers to a group of genetic conditions that affect the adrenal glands. Affected people lack an enzyme the adrenal glands need to make one or more of these hormones and often overproduce androgens. For example, females with a severe form of the condition may have ambiguous genitalia at birth and if not properly diagnosed, develop dehydration, poor feeding, diarrhea, vomiting and other health problems soon after. People with milder forms may not be diagnosed with the condition until adolescence or adulthood when they experience early signs of puberty or fertility problems.

At the 2026 American Association of Clinical Endocrinology (AACE) Annual Meeting, two-year data from the phase 3 CAHtalyst adult clinical trial of crinecerfont was presented. Crinecerfont is a potent and selective oral corticotropin-releasing factor type 1 receptor (CRF1) antagonist designed to reduce and control excess adrenocorticotropic hormone (ACTH) and adrenal androgens through a non-glucocorticoid (GC) mechanism.

The phase 3 CAHtalyst global registrational studies were designed to evaluate the safety, efficacy and tolerability of crinecerfont in children and adults with classic CAH due to 21-hydroxylase deficiency. The CAHtalyst Adult study included 182 adult patients ages 18 to 58 years. The study evaluated improvement of androgen control over four weeks of crinecerfont treatment and the enabling of GC reduction to physiologic range while androstenedione levels were maintained or improved over an additional 20 weeks of treatment.

At month 24 of the study, 69% (n=149) of participants achieved a physiologic GC dose, with many participants eliminating nonphysiologic GC types. Of participants originally taking dexamethasone (n=20), 75% switched to a dexamethasone-free regimen, while 62% (37/60) of patients taking more than two doses of hydrocortisone per day were able to eliminate a dose outright. GC dose reductions and regimen changes were achieved without worsening androstenedione levels relative to baseline, indicating that lowering the GC dose was not achieved at the expense of androgen control.

Long‑term treatment with crinecerfont was generally well tolerated, with more than 80% study retention at two years and no new safety signals observed.

Data from the CAHtalyst phase 3 studies supported approval of crinecerfont by the US Food and Drug Administration in December 2024. The open-label extension treatment portions of both studies are ongoing.  

Chronic exposure to supraphysiologic GC doses is associated with numerous long-term health risks, including cardiometabolic, bone health and quality-of-life complications. Reducing high-dose, long-term GC exposure represents one of the most important goals in the management of classic congenital adrenal hyperplasia (CAH).

To learn more about CAH and other rare endocrine disorders, visit https://checkrare.com/diseases/endocrine-disorders/

CHAPTERS
Introduction 00:00
CAH Overview 00:13
Diagnosis and Current Management 1:50
Two-Year Results 3:10
Weight and Metabolic Outcomes 4:58

0 0

Kinga Tomczak, MD, PhD, Program Director of the Tic Disorders and Tourette Syndrome Program at Boston Children’s Hospital and Assistant Professor of Neurology at Harvard Medical School, discusses phase 3 clinical trial results of ecopipam as a treatment for Tourette syndrome.

Tourette syndrome is a chronic childhood-onset neurodevelopmental disorder characterised by motor and phonic tics that can substantially diminish the quality of life of affected individuals. The underlying pathophysiology of Tourette syndrome is not fully understood, but recent research has brought new insights into the genetic variations and the alterations in neurophysiology and brain networks contributing to its pathogenesis. Tourette syndrome occurs more frequently in males, and males tend to have more severe symptoms than females. Tourette syndrome is often accompanied by comorbid behavioural disorders, including most prominently obsessive-compulsive behaviour and attention deficit disorders.

At the American Academy of Neurology 2026 Annual Meeting (AAN 2026), data was presented from a phase 3 study on the safety and efficacy of ecopipam for the treatment of Tourette syndrome. Ecopipam is a selective dopamine D1 receptor antagonist being investigated as a maintenance therapy in persons with Tourette syndrome.

In the study, patients ages 6 years and older with Tourette syndrome were included in a double-blind, placebo-controlled, randomized withdrawal trial. Ecopipam was titrated over 3 to 4 weeks with a target dose of 1.8 mg/kg/day in the 12 week open-label period. Patients with a clinically meaningful reduction of 25% or greater in Yale Global Tic Severity Scale Total Tic Score (YGTSS-TTS) at weeks 8 and 12 were randomized to continue ecopipam or taper to placebo in the 12 week double-blind period.

A total of 216 patients were enrolled in the 12 week open-label phase. Overall, 104 patients (90 pediatric) were randomized to the 12 week double-blind period to continue ecopipam or switch to placebo. The risk of relapse was significantly reduced in the ecopipam group compared with placebo in the pediatric and pediatric plus adult populations. The most commonly reported adverse events in the ecopipam group during the 24 week study were somnolence, anxiety, headache, insomnia, tic, and fatigue.

Overall, this study demonstrated ecopipam’s ability to maintain clinically meaningful improvements in Tourette syndrome symptoms. It was generally well-tolerated, with adverse events primarily affecting the central nervous syndrome and did not cause weight gain, dyslipidemia, or drug-induced movement disorders.

To read the abstract presented at AAN 2026, visit https://index.mirasmart.com/AAN2026/PDFfiles/AAN2026-004157.html

To learn more about rare neurological conditions, visit https://checkrare.com/diseases/neurology-nervous-system-diseases/

CHAPTERS
Introduction 00:00
Tourette Syndrome Overview 00:21
Developing Treatments 3:46
Ecopipam Clinical Trial Data 5:23
Clinical Trial Design 11:12
Take Home Message 13:28

1 0

Naji Gehchan, MD, MBA, Chief Medical and Development Officer at Kyverna Therapeutics, discusses new follow-up data on KYV-101 treatment for patients with myasthenia gravis (MG).

Generalized MG (gMG) is a chronic autoimmune neuromuscular disease characterized by weakness of the skeletal muscles. Common symptoms include weakness of the muscles that control the eye and eyelid, facial expressions, chewing, talking, and swallowing. The condition results from a defect in the transmission of nerve impulses to muscles due to the presence of antibodies against the acetylcholine receptor. The exact reason this occurs is not known.

An update of KYSA-6 (NCT06193889) a phase 2, open-label, single-arm, multicenter study of KYV-101 in gMG was presented at the 2026 American Academy of Neurology Annual Meeting. KYV-101 is a fully human, autologous CD19 CAR T-cell therapy with CD28 costimulation, designed to achieve deep B-cell depletion and immune reset to deliver durable, drug-free, disease-free remission.

In the study, adults ages 18 to 75 years with gMG (MGFA class IIb-IV), history of AChR or MuSK autoantibodies, MG Activities of Daily Living (MG-ADL) score of 6 or greater, and 2 or more immunosuppressant/immunomodulator failures, received lymphodepletion and a single infusion of 1×10^8 CAR T cells.

As of October 2025, 6 patients were dosed and follow-up ranged from 28 days to 9 months. Robust CAR T-cell expansion and B-cell depletion occurred in all patients. With a single dose, 100% of patients had 3-point or greater improvements in MG-ADL from baseline, with 50% achieving minimal symptom expression at last follow-up. At 24 weeks, KYV-101 treatment resulted in 8.0-point and 7.7-point mean reductions from baseline in MG-ADL and QMG scores, respectively. Of the 6 patients, 5 became nonsteroidal immunosuppressant therapy-free. No ICANS and no high-grade CRS events occurred.

Overall, treatment with KYV-101 resulted in robust and sustained improvements in disease severity with an acceptable safety profile, while eliminating background immunosuppressants in the majority of patients. A phase 3 clinical study is ongoing.

To learn more about gMG and other rare neurological conditions, visit https://checkrare.com/diseases/neurology-nervous-system-diseases/

CHAPTERS
Introduction 00:00
KYV-101 in Myasthenia Gravis 00:10
Next Steps 1:28

0 0