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Disease Profile

Protein S deficiency

Prevalence
Prevalence estimates on Rare Medical Network websites are calculated based on data available from numerous sources, including US and European government statistics, the NIH, Orphanet, and published epidemiologic studies. Rare disease population data is recognized to be highly variable, and based on a wide variety of source data and methodologies, so the prevalence data on this site should be assumed to be estimated and cannot be considered to be absolutely correct.

Unknown

Age of onset

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ICD-10

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Inheritance

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

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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

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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.

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

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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.

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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.

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Not applicable

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Categories

Blood Diseases

Summary

Protein S deficiency is a disorder that causes abnormal blood clotting. When someone bleeds, the blood begins a complicated series of rapid chemical reactions involving proteins called blood coagulation factors to stop the bleeding. Other proteins in the blood, such as protein S, usually regulate these chemical reactions to prevent excessive clotting. When protein S is missing (deficient), clotting may not be regulated normally and affected individuals have an increased risk of forming a blood clot called a thrombosis. People at risk to have protein S deficiency are those with an individual or family history of multiple blood clots in the veins. Treatment may include taking medication known as blood thinners to decrease the chance of developing a blood clot.[1]

Cause

Protein S deficiency is usually hereditary, but may be acquired. The hereditary form of protein S deficiency is caused by a mutation in a gene called PROS1. This condition is inherited in an autosomal dominant manner, which means that an individual who inherits only one mutated copy of PROS1 has an increased chance of developing symptoms of this disease. Individuals who inherit one mutated copy of the PROS1 gene are said to be heterozygotes while those that inherit two mutated copies of the PROS1 gene are called homozygotes. Blood clots (thrombosis) may occur in both heterozygotes and homozygotes; however, homozygotes may develop a severe form of thrombosis called purpura fulminans. Purpura fulminans involves severe clotting throughout much of the body and is a life-threatening condition.

Rarely, protein S deficiency is acquired, meaning it develops as a result of another condition such as liver disease or vitamin K deficiency.[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

  • The Genetic Testing Registry (GTR) provides information about the genetic tests for this condition. The intended audience for the GTR is health care providers and researchers. Patients and consumers with specific questions about a genetic test should contact a health care provider or a genetics professional.

    Treatment

    Treatment of protein S deficiency occurs either in patients who have had a venous thrombosis or in patients with asymptomatic carrier states without a thrombotic event, depending on the decisions made by the patient's health care provider. Following a venous thrombosis, patients are treated with anticoagulant drugs (blood thinners) including heparin followed by warfarin. In most patients, specialists recommend 6-9 months of initial treatment with warfarin. The question of whether to continue lifelong warfarin in patients with identified protein S deficiency after their first thrombotic event is controversial. If the first thrombotic event was life threatening or occurred in multiple or unusual sites (i.e. cerebral veins, mesenteric veins), most experts recommend lifelong therapy initially. If brought about especially abruptly by a strong event (i.e. trauma, surgery) and the thrombosis did not meet the criteria of life threatening or multiple or unusual sites, some experts argue that these patients may have a lower risk of recurrence and deserve a trial without warfarin after 9 months.

    In patients who are asymptomatic carriers of protein S deficiency, the goal of therapy is prevention of the first thrombosis. In such patients, drugs that predispose to thrombosis, including oral contraceptives should be avoided. If these patients require surgery or an orthopedic injury occurs, prophylaxis with heparin may become necessary.[2]

    Organizations

    Support and advocacy groups can help you connect with other patients and families, and they can provide valuable services. Many develop patient-centered information and are the driving force behind research for better treatments and possible cures. They can direct you to research, resources, and services. Many organizations also have experts who serve as medical advisors or provide lists of doctors/clinics. Visit the group’s website or contact them to learn about the services they offer. Inclusion on this list is not an endorsement by GARD.

    Organizations Supporting this Disease

      Organizations Providing General Support

        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

        • MedlinePlus Genetics contains information on Protein S deficiency. This website is maintained by the National Library of Medicine.

          In-Depth Information

          • Medscape Reference provides information on this topic. You may need to register to view the medical textbook, but registration is free.
          • 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. 
          • PubMed is a searchable database of medical literature and lists journal articles that discuss Protein S deficiency. Click on the link to view a sample search on this topic.

            References

            1. Congenital protein C or S deficiency. MedlinePlus. February 2012; https://www.nlm.nih.gov/medlineplus/ency/article/000559.htm. Accessed 3/4/2013.
            2. Mohammad Muhsin Chisti, MD, FACP. Protein S Deficiency. Medscape. Jan 27, 2016; https://emedicine.medscape.com/article/205582.
            3. Lipe B, Ornstein L. Deficiencies of Natural Anticoagulants, Protein C, Protein S, and Antithrombin. Circulation. 2011; https://circ.ahajournals.org/content/124/14/e365.full. Accessed 3/6/2011.
            4. US National Library of Medicine. Protein S Deficiency. Genetics Home Reference. October 2009; https://ghr.nlm.nih.gov/condition/protein-s-deficiency.
            5. Goodwin JE. Protein S Deficiency. Medscape Reference. January 2012; https://emedicine.medscape.com/article/205582-overview.

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