GeneHealth - Your precision medicine

Tangier Disease

Disease Details

Family Health Simplified

Buy Membership

Description: Tangier disease is a rare genetic disorder characterized by significantly reduced levels of high-density lipoproteins (HDL) in the blood, leading to the accumulation of cholesterol in various tissues.
Type: Tangier disease is a rare inherited disorder characterized by severe reduction in the levels of high-density lipoprotein (HDL) or "good" cholesterol in the blood. It follows an autosomal recessive pattern of genetic transmission.
Signs And Symptoms: Individuals that are homozygotes for Tangier's disease develop various cholesterol ester depositions. These are especially visible in the tonsils, as they may appear yellow/orange. The cholesterol esters may also be found in lymph nodes, bone marrow, the liver and spleen.Due to the cholesterol ester depositions the tonsils may be enlarged. Hepatosplenomegaly (enlarged liver and spleen) is common.Neuropathy and cardiovascular disease are the most devastating developments caused by Tangier's disease.
Prognosis: Tangier disease is a rare inherited disorder characterized by a severe reduction in high-density lipoprotein (HDL) cholesterol levels in the blood. The prognosis for individuals with Tangier disease can vary based on the severity and range of symptoms. While some people might remain relatively asymptomatic, others may experience significant complications, including cardiovascular issues, neuropathy, and gastrointestinal problems. Lifespan can be affected depending on the extent of cardiovascular involvement and other associated conditions. Regular monitoring and management by healthcare professionals are essential for optimizing health outcomes.
Onset: Tangier disease is typically characterized by its onset in childhood. The specific age of onset can vary, but symptoms often appear in early childhood or adolescence.
Prevalence: Tangier disease is an extremely rare genetic disorder. Its exact prevalence is unknown, but it has been documented in fewer than 100 cases worldwide.
Epidemiology: Tangier disease is an extremely rare inherited disorder with very few cases reported globally. The exact prevalence is not well documented due to its rarity. The condition has been identified in various populations but was first discovered on Tangier Island in Virginia. It is more frequently studied in areas where consanguinity (marriage between relatives) is common, which can increase the likelihood of genetic disorders.
Intractability: Tangier disease is generally considered intractable because there is currently no cure for the condition. Treatments primarily focus on managing symptoms and preventing complications rather than addressing the underlying genetic cause. This rare genetic disorder affects the body's ability to transport cholesterol, leading to very low levels of high-density lipoprotein (HDL) cholesterol. However, ongoing research may provide more insights in the future.
Disease Severity: Tangier disease is a rare inherited disorder characterized by severely reduced levels of high-density lipoprotein (HDL) cholesterol in the blood. This condition can lead to the accumulation of cholesterol in various tissues, causing symptoms such as enlarged tonsils, peripheral neuropathy, and an increased risk of cardiovascular disease. Severity can vary among individuals, but it often leads to significant health problems and requires ongoing medical care.
Healthcare Professionals: Disease Ontology ID - DOID:1388
Pathophysiology: Pathophysiology of Tangier Disease:

Tangier disease is a rare, inherited disorder characterized by extremely low levels of high-density lipoprotein (HDL) in the blood. This condition is caused by mutations in the ABCA1 gene, which encodes the ATP-binding cassette transporter A1 (ABCA1) protein. The ABCA1 protein is crucial for the transport of cholesterol and phospholipids from cells to the HDL particles.

Mutations in the ABCA1 gene disrupt this transport process, leading to the accumulation of cholesterol and phospholipids within cells, particularly in macrophages. These lipid-laden cells can build up in various tissues, including the liver, spleen, tonsils, and intestinal mucosa, leading to organomegaly, hepatosplenomegaly, and the characteristic orange-yellow tonsils. The diminished HDL levels impair the reverse cholesterol transport mechanism, increasing the risk for atherosclerosis and cardiovascular disease. Tangier disease also leads to peripheral neuropathy and other systemic symptoms.
Carrier Status: Tangier disease is a rare inherited disorder characterized by a severe reduction in high-density lipoprotein (HDL) cholesterol levels. It is inherited in an autosomal recessive manner, meaning that an individual must inherit two copies of the mutated gene (one from each parent) to develop the disease. Carriers, who have just one copy of the mutated gene and one normal gene, typically do not exhibit symptoms of Tangier disease but can pass the mutated gene to their offspring. The primary gene associated with Tangier disease is the ABCA1 gene.
Mechanism: Tangier disease, also known as familial high-density lipoprotein (HDL) deficiency, is a rare inherited disorder characterized by a significant reduction in HDL cholesterol levels.

**Mechanism:**
The disease is caused by mutations in the ABCA1 gene, which encodes the ATP-binding cassette transporter A1 protein. This protein plays a critical role in the transfer of phospholipids and cholesterol from cells to HDL particles, which then transport cholesterol to the liver for excretion. Defective or absent ABCA1 protein results in the impaired formation and maturation of HDL particles, leading to cholesterol accumulation in various tissues.

**Molecular Mechanisms:**
1. **ABCA1 Gene Mutations:** Mutations in the ABCA1 gene disrupt the normal function of the ABCA1 transporter, which impairs the efflux of cholesterol and phospholipids from cells to apolipoprotein A-I (apoA-I) or HDL particles.
2. **Cholesterol Efflux Impairment:** The dysfunction in ABCA1 impairs the initial step in reverse cholesterol transport, where cholesterol from peripheral tissues is transferred to the HDL particles. This defect leads to the accumulation of cholesterol in macrophages and other cells, contributing to the symptoms of the disease.
3. **Reduced HDL Levels:** The defective cholesterol transport mechanism results in extremely low to almost absent levels of HDL cholesterol in the bloodstream. Without adequate HDL levels, the body's capacity to transport cholesterol from tissues to the liver for excretion is severely diminished.
4. **Lipid Deposition:** The impaired cholesterol efflux leads to lipid deposition in various tissues, including the tonsils, liver, spleen, and cornea, contributing to the characteristic clinical features of Tangier disease such as enlarged, yellow-orange tonsils, hepatosplenomegaly, and peripheral neuropathy.

Understanding the molecular mechanisms behind Tangier disease has provided insights into the essential role of the ABCA1 transporter in HDL metabolism and reverse cholesterol transport.
Treatment: There are drugs that can increase serum HDL such as niacin or gemfibrozil. While these drugs are useful for patients with hyperlipidemia, Tangier's disease patients do not benefit from these pharmaceutical interventions.Therefore, the only current treatment modality for Tangier's disease is diet modification. A low-fat diet can reduce some of the symptoms, especially those involving neuropathies.
Compassionate Use Treatment: Tangier disease, a rare genetic disorder characterized by severe reductions in high-density lipoprotein (HDL) cholesterol, currently does not have a specific approved treatment. Management typically focuses on addressing symptoms and preventing complications such as cardiovascular disease.

**Compassionate use treatment:**
- Compassionate use treatments might involve lipid-lowering agents that are not specifically approved for Tangier disease but aim to manage lipid abnormalities and reduce cardiovascular risk. Examples might include statins or other lipid-modifying therapies.

**Off-label or experimental treatments:**
- Off-label treatments could involve medications like niacin or fibrates, which are typically used to manage dyslipidemia but might be considered based on a clinician’s discretion in an attempt to elevate HDL levels.
- Experimental treatments may target the underlying genetic mutation or protein dysfunctions associated with Tangier disease, such as gene therapy or novel agents aimed at increasing HDL cholesterol. These approaches would likely be part of clinical trials.

It is essential for patients with Tangier disease to seek care from healthcare providers experienced in managing rare lipid disorders, as treatment plans need to be highly individualized.
Lifestyle Recommendations: Tangier disease is a rare inherited disorder characterized by significantly reduced levels of high-density lipoprotein (HDL) cholesterol. For individuals with Tangier disease, lifestyle recommendations include:

1. **Healthy Diet**: Adopting a diet low in saturated fats and cholesterol while rich in fruits, vegetables, whole grains, and lean proteins can help manage cholesterol levels.

2. **Regular Exercise**: Engaging in regular physical activity can help maintain a healthy weight and improve overall cardiovascular health.

3. **Smoking Cessation**: Avoiding smoking is crucial as smoking can further lower HDL cholesterol and exacerbate cardiovascular risk.

4. **Regular Medical Check-Ups**: Routine check-ups with a healthcare provider to monitor cardiovascular health and manage any associated conditions.

5. **Medication Adherence**: Following prescribed treatments and medications to manage cholesterol levels and other related health conditions.

6. **Genetic Counseling**: Since Tangier disease is inherited, genetic counseling may be beneficial for affected individuals and their family members.
Medication: Tangier disease is a rare genetic disorder characterized by severe reduction in high-density lipoprotein (HDL) cholesterol levels. There is no specific medication for Tangier disease. Management primarily focuses on addressing symptoms and associated conditions, such as cardiovascular disease. This includes lifestyle changes and treatments aimed at reducing risk factors for heart disease. Regular monitoring by healthcare professionals is essential.
Repurposable Drugs: Currently, there are no well-documented repurposable drugs specifically for Tangier disease. This rare genetic disorder involves the ABCA1 gene, affecting cholesterol and lipid metabolism. Management generally focuses on symptomatic treatment and lifestyle modifications to mitigate cardiovascular risk rather than specific pharmacological intervention.
Metabolites: Tangier disease is a rare inherited disorder where there is a significant reduction in high-density lipoprotein (HDL) cholesterol levels. The primary metabolites associated with Tangier disease include:

1. **Cholesterol esters**: These accumulate in various tissues, including the tonsils, liver, spleen, and lymph nodes.
2. **Triglycerides**: These can be elevated in the blood.
3. **Apolipoprotein A-I (apoA-I)**: Levels are profoundly low or undetectable in patients with Tangier disease.

The most distinguishing metabolic characteristic is the almost complete absence of HDL cholesterol in the blood.
Nutraceuticals: Tangier disease is a rare genetic disorder characterized by significantly reduced levels of high-density lipoprotein (HDL) cholesterol in the blood. Currently, there is limited evidence on the use of nutraceuticals specifically for Tangier disease. Research on nanotechnology applications for this condition is also in its early stages. Management primarily focuses on symptom relief and avoiding complications. Always consult healthcare providers for personalized advice.
Peptides: Tangier disease, also known as Familial High-Density Lipoprotein (HDL) Deficiency, does not directly involve peptides or NAN (not-a-number). The disease is caused by mutations in the ABCA1 gene, which leads to defective cholesterol transport and results in very low to near-absent levels of HDL cholesterol in the blood. This results in the accumulation of cholesterol in various tissues, including the tonsils, liver, spleen, and other organs. Patients often present with orange tonsils, hepatosplenomegaly, peripheral neuropathy, and an increased risk of cardiovascular disease.