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Disease Profile

Tangier disease

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.

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US Estimated

Europe Estimated

Age of onset

Neonatal

ICD-10

E78.6

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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Other names (AKA)

High density lipoprotein deficiency, type 1; HDLDT1; High density lipoprotein deficiency, Tangier type;

Categories

Congenital and Genetic Diseases; Endocrine Diseases; Eye diseases;

Summary

Tangier disease is an inherited disorder characterized by significantly reduced levels of high-density lipoprotein (HDL) the 'good cholesterol' in the blood. Because people with Tangier disease have very low levels of HDL, they have a moderately increased risk of cardiovascular disease. Tangier disease is caused by mutations in the ABCA1 gene. It is inherited in an autosomal recessive pattern.[1]

Symptoms

Tangier disease is characterized by significantly reduced levels of high-density lipoprotein (HDL) the "good" cholesterol in the blood. HDL transports cholesterol and certain fats called phospholipids from the body's tissues to the liver, where they are removed from the blood. Because people with Tangier disease have very low levels of HDL, they have a moderately increased risk of cardiovascular disease. Additional signs and symptoms of Tangier disease include a slightly elevated amount of fat in the blood; disturbances in nerve function; and enlarged, orange-colored tonsils. Affected individuals often develop atherosclerosis, which is an accumulation of fatty deposits and scar-like tissue in the lining of the arteries. Other features of this condition may include an enlarged spleen, an enlarged liver, clouding of the clear covering of the eye, and type 2 diabetes.[1]

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
Hypertriglyceridemia
Increased plasma triglycerides
Increased serum triglycerides
Increased triglycerides

[ more ]

 0002155
Hypocholesterolemia
Decreased circulating cholesterol level
0003146
30%-79% of people have these symptoms
Abdominal pain
Pain in stomach
Stomach pain

[ more ]

 0002027
Accelerated atherosclerosis
0004943
Chronic noninfectious lymphadenopathy
0002730
Coronary artery stenosis
Narrowing of coronary artery
0005145
Distal muscle weakness
Weakness of outermost muscles
0002460
Dry skin
0000958
Ectropion
Eyelid turned out
0000656
Hepatosplenomegaly
Enlarged liver and spleen
0001433
Nail dystrophy
Poor nail formation
0008404
Orange discolored tonsils
0030814
Peripheral axonal neuropathy
0003477
Progressive peripheral neuropathy
0007133
5%-29% of people have these symptoms
Anemia
Low number of red blood cells or hemoglobin
0001903
Carotid artery stenosis
Narrowing of carotid artery
0100546
Corneal opacity
0007957
Facial diplegia
0001349
Impaired thermal sensitivity
0006901
Left ventricular hypertrophy
0001712
Syringomyelia
Fluid-filled cyst in spinal cord
0003396
Thrombocytopenia
Low platelet count
0001873
Percent of people who have these symptoms is not available through HPO
Autosomal recessive inheritance
0000007
Cicatricial ectropion
0025608
Coronary artery atherosclerosis
Plaque build-up in arteries supplying blood to heart
0001677
Decreased HDL cholesterol concentration
Decreased circulating high-density lipoprotein cholesterol
Decreased HDL cholesterol
Low HDL-cholesterol

[ more ]

 0003233
Distal amyotrophy
Distal muscle wasting
0003693
Hepatomegaly
Enlarged liver
0002240
Hyporeflexia
Decreased reflex response
Decreased reflexes

[ more ]

 0001265
Impaired pain sensation
Decreased pain sensation
0007328
Impaired temperature sensation
Abnormality of temperature sensation
Loss of temperature sensation

[ more ]

 0010829
Myocardial infarction
Heart attack
0001658
Nail dysplasia
Atypical nail growth
0002164
Opacification of the corneal stroma
0007759
Peripheral demyelination
0011096
Splenomegaly
Increased spleen size
0001744
Visual impairment
Impaired vision
Loss of eyesight
Poor vision

[ more ]

 0000505
Do you have updated information on this disease? We want to hear from you.

Cause

Tangier disease is caused by mutations in the ABCA1 gene. This gene provides instructions for making a protein that releases cholesterol and phospholipids from cells. These substances are used to make HDL, which transports them to the liver. Mutations in the ABCA1 gene prevent the release of cholesterol and phospholipids from cells. As a result, these substances accumulate within cells, causing certain body tissues to enlarge and the tonsils to acquire a yellowish-orange color. A buildup of cholesterol can be toxic to cells, leading to impaired cell function or cell death. In addition, the inability to transport cholesterol and phospholipids out of cells results in very low HDL levels, which increases the risk of cardiovascular disease. These combined factors cause the signs and symptoms of Tangier disease.[1]

Diagnosis

GeneTests lists laboratories offering clinical genetic testing for this condition. Clinical genetic tests are ordered to help diagnose a person or family and to aid in decisions regarding medical care or reproductive issues. 

Orphanet lists international laboratories offering diagnostic testing for this condition. Click here and scroll down the page to learn more about the processes of certification, accreditation, and external quality assessment available to these labs. Click on Orphanet to view the list.

Talk to your health care provider or a genetic professional to learn more about your testing options.

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.
  • Orphanet lists international laboratories offering diagnostic testing for this condition.

    Treatment

    To our knowledge there is no specific treatment for Tangier disease. Drugs known to increase high density lipoprotein levels in unaffected people, such as estrogens, nicotinic acid, statins, or phenytoin, do not work in people with Tangier disease.[2]

    To reduce the risk for heart and blood vessel disease, people with this condition should maintain a low fat (especially saturated fat) diet and overall healthy lifestyle. Heart disease risk factors such as smoking, high blood pressure, diabetes, obesity, high level of triglycerides and homocysteine in the blood should receive prompt treatment. Fibrates can be used to help lower triglycerides.[2]

    To date, no treatment has been found to prevent the progression of this disease, including trials of omega-3-fatty acids, antioxidants, and vitamin E.[2]

    Individuals with Tangier disease may benefit from referral to specialized lipid centers for advanced management. Consultation with the following specialists may be required:[3]

    • Lipidologist
    • Endocrinologist
    • Cardiologist
    • Vascular specialist
    • Cardiovascular surgeon
    • Dietitian

    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

      • Genetics Home Reference (GHR) contains information on Tangier disease. This website is maintained by the National Library of Medicine.
      • The National Organization for Rare Disorders (NORD) has a report for patients and families about this condition. NORD is a patient advocacy organization for individuals with rare diseases and the organizations that serve them.

        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.
        • 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. 
        • 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 Tangier disease. Click on the link to view a sample search on this topic.

          References

          1. Tangier disease. Genetics Home Reference (GHR). 2010; https://ghr.nlm.nih.gov/condition/tangier-disease. Accessed 8/19/2011.
          2. Assmann G, von Eckardstein A, Brewer HB. Familial analphalipoproteinemia: Tangier disease. In: Scriver et al., eds.. The Metabolic & Molecular Basis of Inherited Disease. 8th Ed. 2001;
          3. Singh VN, Citkowitz E. Low HDL Cholesterol (Hypoalphalipoproteinemia) Treatment & Management. eMedicine. 2009; https://emedicine.medscape.com/article/127943-treatment#showall. Accessed 8/19/2011.

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