Tangier disease is an extremely rare hereditary disease to about 100 documented cases to date. Patients with this disease suffer from a disorder of lipid metabolism and decreased production of HDL cholesterol. Causal therapeutic methods for the treatment of Tangier disease do not yet exist.
What is Tangier disease?
Tangier disease is an extremely rare genetic defect. This defect triggers a disorder of fat metabolism. To date, few more than 100 affected individuals have been reported. In 1961, the first person to describe the disease, D. S. Frederickson, named it after the island of Tangier. At that time, the only patients documented up to that time came from this island. Tangier disease is associated with a disturbed release of cholesterol from the body’s cells. As a result, fewer high-density lipoproteins are formed. These so-called HDL proteins primarily transport cholesterol away. The removal of cholesterol is therefore impaired as a result of the low HDL proteins and the substance is increasingly deposited in the reticular connective tissue. The literature sometimes refers to the hereditary disease as an-α-lipoproteinemia, familial HDL deficiency, or familial hypoalphalipoproteinemia.
Causes
The inherited disease of familial HDL deficiency is inherited in an autosomal recessive pattern. Thus, the disease can only be inherited from two partners with the defect. The causative gene defect is thought to be located on the long arm of chromosome nine and relates to the ABCA 1 gene. This ABCA 1 gene codes for transport proteins that are involved in the excretion of cholesterol from the body’s cells. Medical science distinguishes between carriers of the defect and actual sufferers. If both the mother and the father carry the genetic defect, there is a one in four chance of a sick child being born. The probability for children with the defect is two to four, and the probability for completely healthy offspring, like that for a diseased child, is given as a ratio of one to four.
Symptoms, complaints, and signs
The leading symptom of Tangier disease is yellow-orange skin spots. They are located mainly on the lymphoid organs of the oral and pharyngeal skin. Especially the tonsils are affected by the discoloration due to stored cholesterol. Sometimes they are additionally enlarged along with the rest of the lymphatic oral pharyngeal space. Likewise, enlargement of the internal organs can sometimes occur as part of Tangier’s disease. This mainly refers to enlargements of the liver and spleen or even the pancreas. Sometimes arteriosclerosis, i.e. hardening of the arteries, also occurs due to the low HDL level of the patients. As a result, corneal opacities or anemic blood count changes may develop. Somewhat less frequently, neurological symptoms have been reported in addition to the above-mentioned complaints. Initially, these mainly include muscle weakness and sensory and movement disorders of the arms and legs. The neurological symptoms usually remit, but frequently recur in the course of the disease. They usually affect individual nerves of the peripheral nervous system.
Diagnosis and course of the disease
A physician may first suspect Tangier disease on visual diagnosis. Visual diagnosis typically reveals yellow-orange mucosal changes to him or her. In the serum, total cholesterol, HDL cholesterol, and apolipoprotein A-I serve the physician as indicators of the disease. In lipoprotein electrophoresis, for example, no α- or pre-β-bands are found. Regarding cholesterol levels, values below 100 mg/dl are considered indicative of Tangier disease. HDL cholesterol cannot be detected at all at the same time or shows misstructuring. In addition, low apolipoprotein A-II is often present. Human genetic testing often confirms the diagnosis. Nerve biopsies may be required in forms with neurologic deficits. These biopsies usually show a decrease in myelinated and unmyelinated axons. By and large, a relatively favorable prognosis is given for Tangier disease. If vascular or cardiovascular disease develops in adulthood, the prognosis is somewhat less favorable.
Complications
The most serious complication of Tangier disease is overgrowth of the internal organs.In the course of the disease or already from birth, there is enlargement of the liver and spleen, and rarely also of the pancreas. This causes a number of complaints such as symptoms of poisoning, hormonal fluctuations or metabolic disorders, which in turn are associated with severe complications. If arteriosclerosis is detected, it has usually already developed into permanent damage. In most cases, corneal clouding, anemic blood count changes, and neurological complaints then occur. Typical symptoms include muscle weakness as well as sensory and movement disorders of the arms and legs. If not treated, permanent deformities and serious diseases develop. In the most severe cases, the patient suffers from circulatory collapse or even heart failure and eventually dies. Treatment of the rare hereditary disease is also not without risk. Under certain circumstances, gene therapy can trigger serious illnesses and lead, for example, to cancers such as leukemia. Finally, during viral transduction, there is a risk that the patient will become infected with the virus used as a ferry. Such an infection is usually fatal or at least has serious health consequences.
When should you see a doctor?
In the case of Tangier disease, the affected person is dependent on a visit to a doctor. Only through proper and especially early treatment can further complications and discomfort be avoided. Thereby, an early diagnosis has a positive effect on the further course. Therefore, a doctor should be consulted at the first symptoms of Tangier’s disease. The doctor should be consulted if the affected person suffers from various complaints of the eyes. There is usually a clouding of the cornea on the eye. If these complaints occur without any particular reason and do not disappear on their own, a doctor must be consulted in any case. Furthermore, sudden muscle weakness or disturbances in movement may also indicate Tangier’s disease and should also be checked by a doctor. As a rule, Tangier’s disease can be detected and treated by a general practitioner or by an orthopedist. However, the subsequent course depends greatly on the time of diagnosis, so no general prediction is possible.
Treatment and therapy
To date, hardly any therapeutic measures are available for the treatment of Tangier disease. This is due, on the one hand, to their genetic causes and, on the other, to their rarity, which also limits research. A diet plan is one of few therapeutic approaches for Tangier disease so far. Although a special low-fat diet is recommended for all forms of the hereditary disease, the change in diet does not correspond to a causal therapy. Causal therapy may be conceivable in the future using genetic engineering. This genetic treatment would take place in the context of gene therapy and could possibly replace the defective gene with a healthy one. Gene therapies have already been successfully performed on humans in clinical trials today. On the other hand, several deaths have also been reported in connection with gene therapy studies in living humans. In the face of this, gene therapy is still in its infancy and is currently (as of 2015) one of the most important areas of research in medicine. Because of the rarity of Tangier disease, gene therapy studies directly related to the disease have never been conducted.
Prevention
Tangier disease cannot be prevented. However, expectant parents or couples planning to have children can theoretically have their DNA tested for the genetic defect via a sequence analysis. This at least allows a better assessment of the risk of having a child with Tangier disease.
Follow-up
Since Tangier disease is a very rare hereditary disease and is based on a genetic defect, the options for self-treatment are rather limited. However, dietary measures have been shown to be positively effective in this disease: The diet of the affected person should above all be low in fat. Dietary supplements help to compensate for nutrient deficiencies. Raw vegetables and healthy foods dominate the diet. Heavy foods that could increase cholesterol levels should be avoided as far as possible. Medications that negatively affect cholesterol levels must also be discontinued in consultation with the doctor and replaced with alternative medications.A healthy lifestyle can have a positive influence on the patient’s general well-being. This includes sufficient sleep, moderate sporting activities and the avoidance of stress. Pleasure foods such as alcohol and nicotine should be avoided as far as possible. It is important for sufferers to take their medication in accordance with the doctor’s prescriptions and also to be aware of possible interactions and side effects so that appropriate action can be taken if necessary. A causal treatment for Tangier disease is not yet possible. Various genetic therapies are currently being tested that may promise a cure for this disease in the future. Affected individuals should ask their treating physician about these possibilities so that they may be able to participate in current testing programs.
Here’s what you can do yourself
Individuals suffering from Tangier disease primarily need to take dietary measures. A low-fat diet and the use of dietary supplements are recommended. The diet should consist mainly of raw vegetables and healthy foods. Stimulants such as alcohol, nicotine or caffeine should be avoided, as should particularly heavy foods that raise cholesterol levels. This also includes certain medications that must be discontinued in consultation with the doctor. In addition, general measures such as sufficient exercise, plenty of sleep and avoiding stress are important. Sick people must also take the prescribed medication according to the doctor’s instructions and inform the doctor of any side effects and interactions so that the necessary countermeasures can be initiated at an early stage. In addition, consultation should be made with other specialists, such as nutritional physicians and alternative physicians, who can support the treatment of the pain. To date, Tangier disease cannot be treated causally. However, genetic therapies are currently being tested which may provide a cure in the future. Affected individuals should talk to their primary care physician about these possibilities and, if appropriate, participate in current testing programs.
