Authors: Mekka Garcia, MD  - NYU Grossman School of Medicine
Alison L. Christy, MD, PhD  – Providence Pediatric Neurology at St. Vincent Medical Center—Portland, Oregon  

Reviewed: June 2023 

SUMMARY 

Farber disease (FD) is a rare genetic disorder. It is one of the lysosomal storage disorders. Lysosomes are structures found inside almost every cell of the body. Lysosomes contain enzymes that break down molecules.  

FD is caused by a deficiency in an enzyme called ceramidase. When ceramidase is missing, a fat called ceramide builds up in the skin, brain, and other tissues. This causes damage.  

There are seven major types of FD. They differ in age of onset and severity. Their effect on different parts of the body also varies. A thorough history, clinical examination, and blood tests are all key to diagnosis.  

There is no cure for FD. However, supportive care is available.   

Understanding Farber Disease 

An enzyme is a protein that aids chemical reactions in the body. Ceramidase is a type of enzyme. It breaks down a special type of fat called ceramide. Ceramides are important for cell survival. However, they can cause damage in excess.

Disorder Overview

DESCRIPTION

Farber disease occurs when there is an abnormality in a gene called ASAH1. This gene produces an enzyme called ceramidase.  

When the ASAH1 gene is different, ceramidase may not work properly. There may be a decrease in ceramidase activity. This causes accumulation of fats called ceramides. This occurs under the skin, joints, brain, and other tissues. 

FD is extremely rare. It affects approximately less than 1 in every 1,000,000 births. 

SIGNS AND SYMPTOMS

FD usually presents with three classic symptoms: 

• Swollen or painful joints that limit movement. This can also lead to joint deformities. 
• Bumps or nodules under the skin. 
• A hoarse or weak voice. 

Other symptoms may include: 

• Neurological symptoms. These include: 
  • Problems with swallowing 
  • Increased sleepiness 
  • Shortening of the muscles or tendons around joints 
  • Intellectual disability 
  • Difficulty walking 
  • Loss of speech 
  • Seizures (a burst of electrical activity in the brain that can cause the body to behave abnormally) 
  • Myoclonus (unusual movements characterized by jerking) 

• Respiratory problems. 
• Kidney or heart problems. 
• Failure to thrive. The patient has feeding difficulties. This results in poor weight gain.  

There are seven types of FD. The age of onset and severity depends on the type. How much different tissues in the body are affected depends on the type as well. The seven types are:

CAUSES

FD occurs when there is an abnormality in the ASAH1 gene.  

It is an autosomal recessive disorder. This means that a child with this disorder must inherit one abnormal gene from the mother and one abnormal gene from the father.  

If a child inherits one abnormal gene and one normal gene: 

• They will usually not have symptoms. 
• They will instead be called a “carrier” of the disorder. 

If both parents carry the abnormal gene, the risk of a child having the disorder is 25%, or 1 in 4, with each pregnancy.  

Most cases of SHE occur because of new variations. However, SHE may be inherited from an affected parent. If one parent has SHE, all children have a 50% chance of developing KCNT1-related epilepsy. The type of epilepsy in the child may be either SHE or EIMFS. 

LABORATORY INVESTIGATIONS

The following are key to diagnosis:  

• A thorough history. 
• A clinical examination. 
• Plasma ceramidase enzyme activity testing. A blood test can measure the activity of the enzyme.  
• Genetic testing. This tests for the presence of changes in the ASAH1 gene. This can be done using blood or amniotic fluid.  

TREATMENT AND THERAPIES

Currently, there is no cure for FD. However, supportive care is available. Care includes: 

OUTLOOK

The outlook for FD is variable. It largely depends on the type. Some people will have only mild symptoms. Others may develop severe symptoms in infancy and have a shorter lifespan.

RELATED DISORDERS

Some disorders with similar symptoms include: 

• Lysosomal storage disorders, including Sandhoff disease 
• Juvenile idiopathic arthritis 

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