Tangier disease

What is Tangier Disease?

Tangier disease is an inherited disorder characterized by significantly reduced levels of high-density lipoprotein (HDL) in the blood [12]. HDL, also known as "good cholesterol," plays a crucial role in transporting cholesterol and certain fats called phospholipids from the body's tissues to the liver, where they are removed from the blood [12].

Key Features

The major clinical signs of Tangier disease include severe deficiency or absence of HDL in the circulation, resulting in tissue accumulation of cholesteryl esters throughout the body, particularly in the reticuloendothelial system [13]. This can lead to various complications, including:

• Severe reduction or absence of HDL in the blood
• Accumulation of cholesterol esters in organs such as the liver and spleen
• Enlarged liver and spleen
• Characteristic orange tonsils

Causes

Tangier disease is an inherited condition, first described in two siblings from the Tangier island of Virginia in 1961 [11]. It is caused by a genetic mutation that affects the production or function of HDL.

References

[11] First described in two siblings from the Tangier island of Virginia in 1961. [12] Characterized by significantly reduced levels of high-density lipoprotein (HDL) in the blood. [13] Severe deficiency or absence of HDL in the circulation resulting in tissue accumulation of cholesteryl esters throughout the body.

Symptoms of Tangier Disease

Tangier disease, a rare inherited disorder, presents with variable symptoms depending on the severity and organs involved. The condition is characterized by an extremely low level or absence of high-density lipoprotein (HDL) in the blood.

• Enlarged Tonsils: One of the most distinctive features of Tangier disease is the enlargement of tonsils, which can appear yellow or orange due to fatty deposits accumulating in them [1].
• Hepatosplenomegaly: Enlargement of the liver and spleen (hepatosplenomegaly) is another common symptom [2-4].
• Peripheral Neuropathy: Disturbances in nerve function, leading to peripheral neuropathy, can also occur [3-5].
• Mild Hypertriglyceridemia: A slightly elevated amount of fat in the blood (mild hypertriglyceridemia) is another symptom associated with Tangier disease [4, 7].
• Other Symptoms: Additional symptoms may include anaemia, thrombocytopenia, corneal opacities, skin lesions, and atherosclerosis [8-11].

It's essential to note that the age of onset for these symptoms can vary among individuals. In some cases, symptoms may begin in childhood or early adulthood, while in others, they may not appear until later in life.

References:

[1] Context 1 [2] Context 2 [3] Context 3 [4] Context 4 [5] Context 9 [6] Context 7 [7] Context 8 [8] Context 10 [9] Context 11

Diagnostic Tests for Tangier Disease

Tangier disease, a rare inherited disorder, can be diagnosed through various tests. Here are the key diagnostic methods:

• Genetic Testing: Genetic testing is the most definitive way to diagnose Tangier disease. It involves sequencing the ABCA1 gene, which is responsible for producing the protein that helps remove excess cholesterol from cells [2][3]. This test can confirm the presence of pathogenic mutations in the ABCA1 gene.
• Clinical Evaluation: A clinical evaluation by a doctor may also be used to diagnose Tangier disease. This involves assessing symptoms and physical findings, such as orange-colored pharyngeal tonsils, hepatosplenomegaly, corneal opacity, lymphadenopathy, and low levels of HDL cholesterol [10].
• Blood Tests: Blood tests can also be used to diagnose Tangier disease. These tests typically measure the levels of HDL cholesterol in the blood, which are significantly reduced in individuals with this condition [5][6].

Additional Information

It's worth noting that differential diagnosis is sometimes difficult, and genetic testing may be necessary to confirm the diagnosis [2]. Additionally, other conditions such as familial Apolipoprotein A-I deficiency and LCAT deficiency should also be ruled out during the diagnostic process [4].

References:

[1] Not applicable (no relevant information in search results)

[2] Context 2: When differential diagnosis is difficult, genetic testing for ABCA1 mutations should be performed.

[3] Context 8: Diagnosis of Tangier disease is also achieved through clinical evaluation and can be confirmed through genetic testing involving the sequencing of the ABCA1 gene.

[4] Context 4: The differential diagnosis includes familial Apolipoprotein A-I deficiency, LCAT deficiency...

[5] Context 5: Jul 10, 2017 — Tangier disease is a rare inherited disorder characterized by significantly reduced levels of high-density lipoproteins (HDL) in the blood.

[6] Context 6: Oct 30, 2023 — Tangier disease is an inherited disorder characterized by significantly reduced levels of high-density lipoprotein (HDL) in the blood.

[7] Not applicable (no relevant information in search results)

[8] Context 9: Blood (two 4ml EDTA tubes, lavender top) or Extracted DNA (3ug in EB buffer) or Buccal Swab or Saliva (kits available upon request).

[9] Not applicable (no relevant information in search results)

[10] Context 10: In patients with Tangier disease, major physical findings are orange-colored pharyngeal tonsils, hepatosplenomegaly, corneal opacity, lymphadenopathy, and...

Current Status of Drug Treatment for Tangier Disease

Unfortunately, there is no specific treatment available for Tangier disease that can effectively increase high-density lipoprotein (HDL) levels in individuals with this condition [1][2]. While some drugs have been shown to be ineffective in increasing HDL levels in people with Tangier disease, researchers are exploring alternative therapeutic strategies to manage the symptoms and complications associated with this rare genetic disorder.

Ineffective Treatments

Drugs known to increase HDL levels in unaffected individuals, such as estrogens, nicotinic acid, statins, and others, have been tried in patients with Tangier disease but have not shown significant efficacy [3][4]. These treatments may even be contraindicated or require careful consideration due to potential side effects.

Emerging Therapeutic Strategies

Gene therapy for the ABCA1 gene, which is responsible for generating HDL particles from cellular cholesterol and phospholipids, has been highlighted as a potential avenue for treating Tangier disease [5]. Additionally, researchers are exploring other therapeutic strategies aimed at selectively increasing mature HDL concentration to restore cholesterol efflux.

Current Recommendations

Given the lack of effective treatments, management of Tangier disease typically involves supportive care tailored to individual symptoms and manifestations. This may include surgical removal of enlarged tissues, such as tonsils or spleen, in some cases [6][7]. A low-fat diet can also help reduce liver enlargement and other complications.

Future Directions

Further research is needed to develop effective treatments for Tangier disease. The potential use of miglustat, a drug that may be beneficial in treating nerve damage associated with this condition, warrants further investigation [8].

References:

[1] Context 1 [2] Context 4 [3] Context 5 [4] Context 6 [5] Context 7 [6] Context 10 [7] Context 11 [8] Context 9

The differential diagnosis for Tangier disease includes several conditions that can present with similar symptoms and laboratory findings.

• Familial Apolipoprotein A-I deficiency: This is a rare genetic disorder characterized by extremely low levels of high-density lipoproteins (HDL) in the blood, similar to Tangier disease [8][14].
• LCAT deficiency: LCAT (Lecithin-Cholesterol Acyltransferase) is an enzyme that plays a crucial role in cholesterol metabolism. Deficiency of this enzyme can lead to low levels of HDL and high levels of cholesteryl esters, similar to Tangier disease [4][14].
• Secondary causes of low HDL: Certain medications, such as retinoids and androgenic steroids, can cause a decrease in HDL levels. Additionally, paradoxical response to fibrates, liver failure, or cancer can also lead to low HDL levels, which may be mistaken for Tangier disease [14].
• Hereditary Apolipoprotein A-I deficiency: This is another rare genetic disorder that affects the production of apolipoprotein A-I, leading to extremely low levels of HDL in the blood [14].

It's essential to note that these conditions can have overlapping symptoms and laboratory findings with Tangier disease. Therefore, a comprehensive diagnostic workup, including genetic testing, is necessary to confirm the diagnosis.

References:

[8] Diagnostic criteria for Tangier disease are given in Table 1 and the flow chart for differential diagnosis of hypo-HDL-cholesterolemia is shown in Fig.5, based on discussions by the Committee on Primary Dyslipidemia under the Research Program on Rare and Intractable Diseases of Japan’s Ministry of Health, Labour and Welfare.

[14] What Is the Differential Diagnosis of Tangier Disease? The differential diagnosis includes hereditary Apolipoprotein A-I deficiency, LCAT deficiency, and secondary reasons for abnormally low levels of HDL cholesterol, such as medicines retinoids, androgenic steroids, paradoxical response to fibrates, liver failure, or cancer.