Dorfman-Chanarin syndrome is a genetic metabolic disorder that affects the storage of triglycerides. This syndrome belongs to the so-called storage disorders. Because of its genetic basis, causal treatment of the disease is not possible.
What is Dorfman-Chanarin syndrome?
Dorfman-Chanarin syndrome is an extremely rare storage disorder with abnormal storage of triglycerides (neutral fats) in various cells of the body. Thus, fats are stored mainly in fibroblasts, liver cells, muscles, nerve cells, and leukocytes. However, triglyceride degradation no longer takes place there. According to general estimates, the frequency of this disease is 1 in 1 million. So far, only 50 cases have been described worldwide. Most of those affected come from India and the Middle East. The storage disorder is accompanied by ichthyosis (fish scale disease). Sometimes this is the only symptom. However, the disorder must be distinguished from other forms of neutral lipid storage disorders. There are also neutral lipid storage disorders without ichthyosis but with myopathy, which are also referred to as NLSDM. However, Dorfman-Chanarin syndrome is a neutral lipid storage disorder with ichthyosis and is also referred to as NLSDI. The syndrome was first described by dermatologist Dorfman in 1974. Other names for this disorder are Chanarin-Dorfman syndrome, lipidosis with triglyceride storage disease, myopathy with neutral fat storage, or neutral fat storage disease. The disease is present from birth. However, despite some physical limitations, the life expectancy of affected individuals is often not reduced.
Causes
The cause of Dorfman-Chanarin syndrome may be a mutation in the ABHD5 gene. Several mutations of this gene have been identified that render the enzyme for the breakdown of neutral fats nonfunctional. The disease is inherited in an autosomal recessive manner. There are individual descriptions of cases where, for example, relative marriages have led to the expression of this syndrome. The cause of the symptoms of the disease is an abnormal accumulation of neutral fats (triglycerides) in the leukocytes, nerve cells, fibroblasts, liver cells and muscle cells. Either the triglyceride-degrading enzyme is absent or its function is impaired. As a result, neutral fats can no longer be broken down. These accumulate in the corresponding cells and cause functional disorders of the corresponding organs. Where possible, the excess fat is transported out of the cells and removed from the body via the intestines in the form of fatty stools. However, most fat is permanently stored and alters the functioning of the cells. For example, lipid storage in keratinocytes disrupts the skin‘s natural permeability barrier. To compensate, new keratinocytes are constantly produced, eventually leading to a fish scale-like thickening of the skin. In this way, a certain barrier is established, but the skin can no longer properly perform its normal function of heat exchange.
Symptoms, complaints and signs
Dorfman-Chanarin syndrome mainly manifests itself as congenital ichthyosis affecting all parts of the skin. In this condition, the skin layer is thickened by hyperkeratosis and forms a scaly body surface. The skin is also reddened with inflammation. Sometimes ichthyosis remains the only symptom of the disease. However, over time, dysfunction of other organs often develops. Due to fat storage in the liver, hepatosplenomegaly (enlargement of the liver due to fat storage) develops. Furthermore, a leukocyte anomaly (Jordans anomaly) with progressive [[muscle wasting [muscular dystrophy]] occurs.] Fats are also deposited in the eyes, leading to cataract and nystagmus. Involvement of the nervous system causes deficiencies, motor dysfunction, and hearing loss. Ataxia usually develops after middle age. Patients often also suffer from short stature. Fats stored in the liver cause so-called fatty stools.
Diagnosis
When Dorfman-Chanarin syndrome is diagnosed, other diseases also associated with ichthyosis must first be clarified by differential diagnosis. Blood cholesterol and lipid levels are usually normal. Only liver values and muscle enzymes may be elevated.In addition, granulocytes can be examined histologically by lipid staining.
When should you see a doctor?
If other symptoms are added to the characteristic hyperkeratosis, a physician should be consulted in any case. Dysfunctions of other organs as well as disorders of the nervous system require rapid clarification. Anyone who notices the first signs of motor disorders or hearing loss is best advised to speak to the appropriate medical professional. Symptoms of cataract and nystagmus as well as regular fatty stools are also typical warning signs that Dorfman-Chanarin syndrome is taking a severe course. Even if these secondary symptoms are absent, the metabolic disorder should be seen regularly by a physician. The physician must monitor the course and ensure that it is positive. In addition, the medication must be adjusted occasionally, which only the doctor can do. Above all, ichthyosis, which is present from the beginning, must be treated permanently to prevent infections, itching and other unpleasant skin reactions. If bleeding or infections develop, a doctor must be consulted. In addition, if symptoms are severe, emergency medical services or the nearest hospital can be contacted.
Treatment and therapy
Treatment of Dorfman-Chanarin syndrome can only be symptomatic, as it is a genetic condition. To prevent further fat storage, affected individuals are advised to follow a low-fat, high-protein diet. Furthermore, additional triglycerides with medium chain fatty acids should be supplemented. This cannot cure Dorfman-Chanarin syndrome, but it can slow its progression. All other treatments are related to symptom relief. Initially, the main symptom is ichthyosis. As with all ichthyoses, its treatment is very complex. It is important to apply cream and bathe the skin frequently. Furthermore, keratolytics are used, which soften the cornea and make it easier to remove. In most cases of ichthyosis, urea has proven to be an effective keratolytic. Urea is applied in the form of creams and ointments containing urea. If the treatment of the skin is neglected, painful cracks form in the dry skin, which further limits its function. However, the severe forms of ichthyosis can be treated with systemic retinoid therapy, which involves both keratolytic and cornification-inhibiting processes. However, irreversible side effects may occur with this treatment. With the help of these therapies the desquamation of the skin and its defense against infections can be supported. However, causal treatment of Dorfman-Chanarin syndrome is not possible.
Outlook and prognosis
Dorfman-Chanarin syndrome is a genetic disorder. For this reason, causal therapy for this disease is usually not possible, so patients are always dependent on symptomatic treatment. The symptoms are very diverse and become more severe if no treatment is given. Hearing and vision problems occur, and most affected individuals also suffer from reduced intelligence and inferior aptitude. Likewise, many patients suffer from short stature and motor disorders. The child’s development is considerably slowed and limited by Dorfman-Chanarin syndrome, resulting in complications even in adulthood. The therapy is based on the exact symptoms and mainly aims at the ordinary development of the child. With the help of intensive therapies and various support measures, the motor disorders can be remedied. The reduced intelligence can also be limited. However, a complete cure is not achieved in this process. With the help of various creams, the skin complaints can also be alleviated, so that the quality of life of the affected person is increased. Dorfman-Chanarin syndrome does not usually have a negative effect on life expectancy. However, it can cause severe psychological distress in parents or family members.
Prevention
Because Dorfman-Chanarin syndrome is a genetic disorder, there are no preventive measures to prevent it. However, it is important to treat ichthyosis that is already present from the beginning on a permanent basis to prevent infections and unpleasant skin reactions.
Aftercare
As a rule, no special or direct measures or options for aftercare are available to the person affected by Dorfman-Chanarin syndrome. In this syndrome, early detection and treatment of the symptoms is primarily necessary to prevent further complications or further worsening of the symptoms. Since this is also a genetic disease, there is no complete cure. If the patient wishes to have children, genetic counseling may be helpful to possibly prevent inheritance of Dorfman-Chanarin syndrome. In most cases, patients are dependent on taking medications and continue to use creams and ointments. Regular intake and also correct dosage must be ensured in order to permanently alleviate the symptoms. The symptoms should be checked by a doctor at regular intervals. Since Dorfman-Chanarin syndrome can also often lead to psychological upsets, intensive discussions with friends or with the patient’s own parents are also very useful. As a rule, Dorfman-Chanarin syndrome does not reduce the patient’s life expectancy.
What you can do yourself
Dorfman-Chanarin syndrome is an extremely rare inborn error of metabolism associated with abnormal storage of triglycerides. The disease is genetic, and the patient cannot take self-help measures that are causative. However, he can help to alleviate the symptoms. This is particularly true in the case of ichthyosis (fish scale disease), which almost always occurs. The affected skin must be cared for very carefully. Good results are achieved with warm baths enriched with salt from the Dead Sea. After bathing, the skin must be thoroughly dried and creamed. Ointments containing the active ingredient urea are particularly effective, as it has a horn-dissolving effect. Under no circumstances should the patient skip the daily skin care routine. Neglecting the affected skin areas very quickly leads to an aggravation of the symptoms. Painful or bleeding cracks and fissures often form, which are associated with an increased risk of secondary infections. In these cases, a physician should always be consulted immediately. Although the abnormal storage of triglycerides in the body cannot usually be prevented by an adequate diet, it can at least be greatly alleviated. Patients should prefer a low-fat, vitamin-rich diet. Patients are best advised by an ecotrophologist in making the necessary dietary changes.