Rare Endocrinology News

Disease Profile

Pure autonomic failure

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.
1-9 / 1 000 000

331 - 2,979

US Estimated

1-9 / 1 000 000

514 - 4,622

Europe Estimated

Age of onset

Adult

ageofonset-adult.svg

ICD-10

G90.3

Inheritance

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

no.svg

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

no.svg

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.

no.svg

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

no.svg

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.

no.svg

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.

no.svg

Not applicable

notapplicable.svg

Other names (AKA)

Bradbury Eggleston syndrome; Bradbury-Eggleston syndrome; Orthostatic hypotension (a symptom);

Categories

Nervous System Diseases; RDCRN

Summary

Pure autonomic failure (PAF) is a neurodegenerative disease of the autonomic nervous system, which regulates body processes like blood pressure and breathing rate. PAF usually affects only the peripheral autonomic nervous system, which means it does not usually involve the brain and spinal cord (the central nervous system). Symptoms begin in midlife, although they can begin earlier. The main symptom of PAF is orthostatic hypotension, a sudden drop in blood pressure upon standing. This can cause dizziness, lightheadedness, blurry vision, and weakness. Other symptoms can include fatigue, bladder problems, constipation, abnormal sweating, and sleep disorders. The symptoms of PAF tend to get worse over time, and sometimes, PAF can lead to other conditions such as Parkinson's disease, dementia with Lewy bodies, or multiple system atrophy.

The cause of PAF is not known. The symptoms are caused by abnormal accumulations of protein, called Lewy bodies, in the cells of autonomic nerves. The Lewy bodies restrict the production and release of norepinephrine from nerve cells, which in turn causes hypotension. Diagnosis of PAF is based on the symptoms, clinical examination, and a thorough neurological examination. Testing may involve tilt table testing, 24-hour blood pressure monitoring, hyperventilation testing, and a norepinephrine blood test. Treatment is focused on managing the symptoms. Options include both lifestyle changes and medications.[1][2][3][4][5]

Symptoms

The following list includes the most common signs and symptoms in people with pure autonomic failure (PAF). These features may be different from person to person. Some people may have more symptoms than others, and symptoms can range from mild to severe. This list does not include every symptom or feature that has been described in this condition.

Symptoms of pure autonomic failure may include:

  • A sudden drop in blood pressure when a person stands up (orthostatic hypotension)
  • Lightheadedness, dizziness, blurry vision
  • Fatigue
  • Palpitations, anxiety
  • High blood pressure when lying down (supine hypertension)
  • Abnormal sweating

Other symptoms of PAF may include dry mouth, diarrhea or constipation, neck pain, changes in urinary habits, impaired sense of smell, and erectile dysfunction in men. Symptoms begin in middle age and slowly get worse over time. Sometimes PAF leads to other conditions such as Parkinson's disease, dementia with Lewy bodies, or multiple system atrophy.[3][4][5]

This table lists symptoms that people with this disease may have. For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed. This information comes from a database called the Human Phenotype Ontology (HPO) . The HPO collects information on symptoms that have been described in medical resources. The HPO is updated regularly. Use the HPO ID to access more in-depth information about a symptom.

Medical Terms Other Names
Learn More:
HPO ID
80%-99% of people have these symptoms
Abnormality of circulating catecholamine level
0012099
Anhidrosis
Lack of sweating
Sweating dysfunction

[ more ]

0000970
Orthostatic hypotension
Decrease in blood pressure upon standing up
0001278
30%-79% of people have these symptoms
Constipation
0002019
Dysuria
Painful or difficult urination
0100518
Syncope
Fainting spell
0001279
Urinary incontinence
Loss of bladder control
0000020
5%-29% of people have these symptoms
Impotence
Difficulty getting a full erection
Difficulty getting an erection

[ more ]

0000802

Treatment

FDA-Approved Treatments

The medication(s) listed below have been approved by the Food and Drug Administration (FDA) as orphan products for treatment of this condition. Learn more orphan products.

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

    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, a Web site designed by the National Library of Medicine Web site to help you research your health questions, provides more information about autonomic nervous system disorders in general. Click on the link to view this information.
    • The Merck Manuals Online Medical Library provides information on this condition for patients and caregivers.

      In-Depth Information

      • Medscape Reference provides information on this topic. You may need to register to view the medical textbook, but registration is free.
      • MeSH® (Medical Subject Headings) is a terminology tool used by the National Library of Medicine. Click on the link to view information on this topic.
      • 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.
      • Orphanet is a European reference portal for information on rare diseases and orphan drugs. Access to this database is free of charge.
      • PubMed is a searchable database of medical literature and lists journal articles that discuss Pure autonomic failure. Click on the link to view a sample search on this topic.

        References

        1. Brown TP. Pure autonomic failure. Pract Neurol. October, 2017; 17(5):341-348. https://www-ncbi-nlm-nih-gov.ezproxy.nihlibrary.nih.gov/pubmed/28717053.
        2. Thaisetthawatkul P. Pure Autonomic Failure. Curr Neurol Neurosci Rep. August, 2016; 16(8):74. https://www.ncbi.nlm.nih.gov/pubmed/27338613.
        3. Coon EA, Singer W, Low PA. Pure Autonomic Failure. Mayo Clin Proc. Oct 2019; 94(10):2087-2098. https://pubmed.ncbi.nlm.nih.gov/31515103/.
        4. Kaufmann H, Norcliffe-Kaufmann L, Palma JA, Biaggioni I, Low PA, Singer W, at al. Autonomic Disorders Consortim. Natural history of pure autonomic failure: A United States prospective cohort.. Ann Neurol. Feb 2017; 81(2):287-297. https://pubmed.ncbi.nlm.nih.gov/28093795/.
        5. Kabir MA, Chelimsky TC. Pure autonomic failure. Handb Clin Neurol. 2019; 161:413-422. https://pubmed.ncbi.nlm.nih.gov/31307617/.

        Rare Endocrinology News