Farber Disease - An Overview

Introduction

Farber disease is a hereditary lipid storage disorder in which an abnormally large quantity of fat accumulates in the joints, tissues, and central nervous system. Farber disease symptoms include hoarseness or a faint cry, tiny fat lumps under the skin and in other tissues (lipo granulomas), and swollen and painful joints. Breathing difficulties, an enlarged liver and spleen (hepatosplenomegaly), and developmental delays are all possible signs. The symptoms worsen over time, leading to a shorter lifetime. Farber disease is categorized into different categories according to severity and nervous system involvement. Farber disease is caused by a faulty ASAH1 gene and is inherited in an autosomal recessive way. The clinical exam, symptoms, enzyme, and genetic testing are used to make the diagnosis.

What Is Farber Disease?

A lack of the acid ceramidase enzyme results in Farber disease, an extremely rare, progressive, autosomal recessive lysosomal storage disorder. Ceramide is converted to sphingosine and fatty acid by the enzyme acid ceramidase. When the enzyme is lacking, fatty material (also known as ceramide) builds up in the lysosomes of the cells. Additionally, excessive levels of lipids (oils, fatty acids, and related substances) accumulate to hazardous levels in the joints, tissues, and central nervous system. The signs and symptoms of this condition may also be caused by damage to the liver, heart, and kidneys.

What Causes Farber Disease?

Farber disease is an inherited autosomally recessive condition. The affected person inherits the defective gene in one copy from each parent. One copy of the gene that works normally and one copy that does not exist in each parent is referred to as a carrier. There is a 25 percent probability that siblings of people with Farber illness will also have the condition; there is a 50 percent possibility that they will be carriers like their parents; and there is a 25 percent chance that they will be unaffected and not a carrier. Variants in the ASAH1 gene are responsible for farber disease. This gene produces the enzyme acid ceramidase. Two copies of this gene are defective in farber disease patients, which results in an enzyme deficit.

What Are the Symptoms Associated With Farber Disease?

The most typical signs include:

• Subcutaneous nodules, lipogranulomas, and granulomas are lumps that develop beneath the skin at pressure sites and joints.

• Contracture (permanent tightening of the muscles, tendons, and skin) is caused by swollen, aching joints that are gradually losing their range of motion.

• Squeaky voice or crying.

• Pain, particularly in the joints.

• Persistent or recurrent fever.

• The presence of inflammation throughout the body can be detected through blood tests like the erythrocyte sedimentation rate (ESR) or C-reactive protein (CRP).

• Underdevelopment, such as having trouble gaining weight or being short in stature.

Some people with Farber illness also exhibit the following additional symptoms:

• Lung infections, difficulty breathing, and other respiratory conditions are examples of respiratory diseases.

• Central nervous system disorders include seizures, muscular weakness, and developmental delays.

• Liver and spleen enlargement that a doctor might feel or detect via ultrasound.

• Abnormalities to the eye noted by an ophthalmologist (such as cherry-red dots)

• Persistent inflammation.

• Lack of success.

• Bone disorders include peripheral osteolysis, osteoporosis, and bone degradation around joints.

• Extra-large liver (hepatomegaly).

• Arthritis.

• Swollen lymph node.

• Difficulties in swallowing.

• Increased sluggishness and fatigue.

• Significantly diminished mental capacity.

• The course and severity of Farber disease differ significantly. Babies or newborns with severe illnesses often show signs very away and pass away at a very young age.

• Some Farber illness patients may go years without experiencing any symptoms and live to be quite old. Juvenile idiopathic arthritis or other arthritis is frequently misdiagnosed in Farber disease patients.

How to Diagnose Farber Disease?

The diagnosis is made based on clinical and laboratory results by measuring the activity of acid ceramidase in cultured skin fibroblasts, lymphoid cells, or peripheral blood leukocytes. As an alternative, the concentration of ceramide in tissues or cultured cells can be measured, and the lysosomal ceramide catabolism of cultured live cells can be observed. Molecular genetic testing frequently identifies mutations in the ASAH1 gene and permits confirmation of the diagnosis.

What Are the Treatment Modalities Associated With Farber Disease?

Farber disease does not have a specific treatment. In some patients, anti-inflammatory drugs, notably Tocilizumab (an interleukin-6 receptor inhibitor), have been proven to reduce inflammation and discomfort. In patients with few or no lung or nervous system issues, bone marrow transplantation may relieve granulomas (small masses of inflamed tissue) and inflammation. Physical therapy, breathing support, and mobility assistance may be necessary as supportive therapies. Granulomas in the elderly may be surgically reduced or eliminated.

The prognosis of this disease is not good. Farber illness is fatal in children as young as two to three years old. It is unknown how long people with mild or attenuated types will live. The oldest reported Farber illness patients were in their 50s and 60s.

Conclusion

Farber illness is a rare, progressive disease caused by an enzyme termed acid ceramidase deficiency (reduced function). In addition to Farber disease, other names for the condition include acid ceramidase deficiency, Farber lipogranulomatosis, and ASAH1-related disorder. Both men and women are affected by the condition. Moderately reduced mental function and swallowing difficulties may be classic form symptoms. Other signs and symptoms may include vomiting, hoarseness, swelling of the joints and lymph nodes, persistent shortening of muscles or tendons surrounding joints, arthritis, and nodules under the skin. Though it is more common for the disease to start in early infancy, it can also start later in life. Autosomal recessive inheritance patterns are present. Affected families should be offered genetic counseling and told that there is a 25 percent chance of passing the disease on if both parents are carriers but not affected. Aside from analgesics, corticosteroid therapy, and cosmetic surgery, there is presently no particular effective therapy for Farber disease. However, patients with minimal neurological impairment may benefit from allogeneic hematopoietic stem cell transplantation. To know more about this condition, consult the doctor online.