Current Management

Описание: 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.