Farber disease is a very rare metabolic disorder that causes severe physical impairment and leads to death. Newborns only develop the disease if both parents are carriers of the same defective gene. Since there is no specific therapy for the disease, it is currently incurable.
What is Farber disease?
Farber disease is an incurable metabolic disease. In medicine, there are several names for this disease: Farber disease, Farber syndrome, ceramodase deficiency, or disseminated lipogranulomatosis. Farber syndrome is named after the American pathologist Sidney Farber (1903-1973), who discovered the disease and described it. This disease is a genetic lysosomal disorder. The intracellular disorder in the lysosomes results from a genetic defect that is responsible for long-term storage of harmful waste products in the body. Since there are only a few Farber patients worldwide, the disease is still not well understood. Patients usually die in infancy, but usually before the age of three.
Causes
The cause of Farber disease is a mutation of the ASAH gene. The mutation is transmitted autosomal recessively from the parental generation to the offspring. The ASAH gene is encoded for the enzymes ceramidase and acid ceramidase. However, if the gene is mutated, there is a lack of activity of ceramidase and acid ceramidase. Acid ceramidase is an enzyme responsible for lysosomal hydrolase. With the participation of the enzyme ceramidase, hydrolase is a catalysis in which the lipid ceramide is cleaved into the amino alcohol sphingosine and fatty acid. In Farber patients, precisely this process is disturbed. Thus, the starting product ceramide remains un-cleaved in the cells and is stored there in the long term. In its original state, ceramide is a waste product for the body because the genetic defect prevents it from being processed into the necessary end product. Therefore, Farber syndrome belongs to the metabolic diseases. As a result of metabolic disorders, different symptoms can occur, which vary from patient to patient. Also, in Farber’s disease, the time of onset of the signs of the disease varies greatly: in some patients, the first symptoms appear in infancy, while in others, the symptoms appear in infancy. In rare cases, the disease does not become apparent until after puberty.
Symptoms, complaints, and signs
The course of the disease varies widely. When the first signs of the disease appear in infancy, they usually first manifest themselves in the motor disorder. For example, babies cannot extend their limbs or legs and are very limited in their movement. The joint contractures can also cause pain, which requires treatment with painkillers. In addition, periarticular nodules may form in the organs or joints at a very early age. Nodules located just under the skin are also visible to the naked eye. In infants, a change in the larynx is also typical of Faber disease. The generic term for the laryngeal change is laryngomalacia. In the worst case, the laryngeal change leads to narrowing of the airways with respiratory infections and oxygen deficiency, as well as impaired feeding with growth disturbance. However, short stature is also a typical sign of Faber disease independent of laryngomalacia. Other signs of Faber disease include corneal opacity and neurologic abnormalities. It is not uncommon for the spleen and liver to enlarge. Hepatosplenomegaly is said to occur when both organs are enlarged at the same time. Death may occur as early as 1 year of age if the disease progresses aggressively or if diagnosis is delayed.
Diagnosis
Farber syndrome can be detected and diagnosed very quickly. Diagnosis is made either by measuring the enzyme activity of ceramidase or by measuring ceramide degradation. Ceramide degradation occurs in leukocytes or cultured skin fibroblasts. Prenatal diagnostics can also be performed in cases of suspicion, such as when the disease is known to exist in an ancestor.
Complications
In most cases of Farber disease, death occurs. Treatment of the disease is not possible.The complications that occur in the course of the disease vary greatly. However, symptoms already occur in early childhood, so that patients can no longer move their limbs properly. This results in severe limitations in everyday life. The patient is dependent on help from other people. In many cases, pain also occurs, although this can be treated with the help of pain therapy. Due to changes in the larynx, there is an increased risk of respiratory infection, which can lead to death. Short stature also occurs more in Farber’s disease, making the patient’s life more difficult. Furthermore, the liver and spleen may be enlarged. Treatment of the disease is not possible. In most cases, painkillers are used to make daily life bearable. In case of malformations or deformations, surgical interventions can be used, alleviating the disease. In this case, there are no further complications. Bone marrow transplantation can limit symptoms as well, but a complete cure for Farber’s disease is not possible.
When should you see a doctor?
Unfortunately, Farber disease cannot be treated or prevented directly. It eventually leads to the death of the child before reaching the age of one. In this case, the medical doctor should be consulted if the child suffers from motor and mental limitations. The child’s movement is also significantly restricted. Due to the severe pain, many children cry continuously and small lumps form under the skin. Furthermore, medical treatment is necessary for respiratory infections. These become noticeable by heavy breathing of the child. Furthermore, there is also short stature and general disturbances of development and growth. Farber’s disease can be diagnosed by a general practitioner or by a pediatrician. However, further treatment is then carried out by various specialists. Furthermore, many parents and relatives are also dependent on psychological treatment. This can also be requested directly in a hospital. If the symptoms of Farber’s disease occur acutely and endanger the life of the child, an emergency doctor must be notified in any case.
Treatment and therapy
There is no effective therapy for Farber’s disease yet. The symptoms are treated symptomatically with analgesics and glucocorticoids. The latter inhibit inflammatory reactions and help control cellular metabolism. With the help of plastic surgery, severe deformities in the body can be corrected. In these ways, the symptoms are alleviated. To some extent, the treatments make the patients’ lives easier. However, the disease progresses over time. Currently, bone marrow transplantation holds promise for mitigating and improving the disease. There are 50 known cases worldwide in which bone marrow transplantation has been successfully performed. Whether the procedure can cure the disease in the long term remains unclear at this time.
Outlook and prognosis
Farber disease has a very unfavorable prognosis. The disease occurs only in very rare cases but results in premature death in every documented patient to date. Affected patients have parents who both have the same genetic defect. The ASAH gene is mutated in both the biological father and the biological mother. This means that the defective gene is already transmitted in the womb during the development process of the unborn child. As a result, the newborn child inevitably suffers from a severe metabolic disorder. The disorder is not curable due to the lack of medical options. For legal reasons, researchers and scientists have so far not been allowed to interfere with human genetics. This also applies to severe diseases. Therefore, the researched and tested drugs, therapies as well as treatment methods are based on the occurring symptoms of the patient. Despite all efforts, there is no sufficient medical care or alternative healing method so far that leads to a reduction of the symptoms or a long-term relief of existing symptoms. To date, patients with Farber’s disease die within the first few years of their lives. Since in most cases death occurs in the third year of life, they are not expected to reach preschool age.
Prevention
Prevention of Farber’s disease is not possible because the disease, is inherited in an autosomal recessive manner. Autosomal recessive inheritance means that both parents must carry the mutated gene for the child to develop the disease. In addition, the defective allele must be located on both homologous chromosomes. This is why Morbus disease is so rare. And it can skip several generations until another newborn family member becomes ill. Offspring of Faber disease patients have about a 25 percent chance of developing the disease. Although parents can pass the disease on to their children due to a genetic defect, the children themselves are usually healthy. And if only one parent is a carrier of the defective gene, their own children remain healthy, but they can pass the defective gene on to their offspring.
Follow-up
Ovarian cancer follow-up after therapy is completed focuses on detecting tumor recurrence, monitoring and treating side effects of therapy, helping patients with psychological and social problems, and improving and maintaining quality of life. Following therapy, check-ups with a gynecologist are recommended every three months. How long the check-ups are necessary depends on the assessment of the treating physician. Normally, the gynecologist begins the check-up with a detailed discussion, in which psychological, social and sexual problems are relevant in addition to physical complaints. After that, the gynecologist usually performs a gynecological examination and an ultrasound examination. Patients who do not experience any particular symptoms do not require any further special examinations. If symptoms occur during the course of the procedure, such as an increase in abdominal girth due to water retention or shortness of breath, further examinations, including CT, MRI or PET/CT, may be useful. Complaints that occur during the course of the disease should be taken seriously by affected patients and discussed with the treating gynecologist. The therapy of ovarian cancer often includes radical surgery. Therefore, the control examinations should be used to be able to recognize and treat possible consequences of the operation at an early stage. Any side effects of necessary chemotherapy can also be monitored by regular check-ups.
What you can do yourself
Faber disease is a very rare hereditary metabolic disorder that is considered incurable and very often leads to death in childhood. Because the disease is genetic, those affected cannot take self-help measures that have a causative effect. Couples in whose families Faber syndrome has already occurred can seek human genetic counseling before starting a family. During this consultation, they will be informed about the likelihood that their offspring will suffer from this disorder and what stresses they will have to be prepared for in this case. Children suffering from Faber’s disease very often die as infants. The affected parents must expect that their child will not reach the age of three. Families should not bear this enormous emotional burden alone. Relatives are advised to consult a psychotherapist after the diagnosis. Many parents also find it helpful to talk to other families in a similar situation. Since Faber disease is very rare, there are no specific support groups. However, relatives of children with severe cancer face similar stresses. Membership in such groups can therefore be helpful in working through the everyday stresses and coping better with the help of others affected.
