Farber disease

Title

Other Names:

Farber lipogranulomatosis; Ceramidase deficiency; Acid ceramidase deficiency; Farber lipogranulomatosis; Ceramidase deficiency; Acid ceramidase deficiency; AC deficiency; N-Laurylsphingosine deacylase deficiency; Farber's disease See More

Categories:

Congenital and Genetic Diseases; Eye diseases; Metabolic disorders; Congenital and Genetic Diseases; Eye diseases; Metabolic disorders; Nervous System Diseases; Skin Diseases See More

This disease is grouped under:

Sphingolipidosis

Summary Summary

Farber disease is an inherited lipid storage disease in which an excess amount of fat builds up in the joints, tissues, and central nervous system. Symptoms of Farber disease include a hoarse voice or weak cry, small lumps of fat under the skin and in other tissues (lipogranulomas), and swollen and painful joints. Other symptoms may include difficulty breathing, an enlarged liver and spleen (hepatosplenomegaly), and developmental delay. The symptoms tend to get worse over time and lead to a shortened lifespan. There are multiple types of Farber disease classified by the severity and nervous system involvement. Farber disease occurs when the ASAH1 gene is not working correctly and is inherited in an autosomal recessive pattern. It is diagnosed based on clinical exam, the symptoms, and enzyme and genetic testing. Treatment is focused on managing the symptoms. Stem cell transplant is an option for some patients.^[1]^[2]^[3]

Last updated: 6/12/2020

Symptoms Symptoms

The following list includes the most common signs and symptoms in people with Farber disease. These features may be different from person to person. Some people may have more symptoms than others and symptoms can range from mild to severe. This list does not include every symptom or feature that has been described in this condition

Signs and symptoms of Farber disease may include:^[1]^[2]

Joint pain and swelling (arthralgia)
Failure to thrive
Enlarged liver (hepatomegaly)
Hoarse cry due to a soft, floppy voice box (laryngomalacia)
Lumps of fat under the skin and around the joints (periarticular subcutaneous nodules)
Short stature
Developmental delay

Symptoms typically appear in the first few weeks of life. In severe cases, both the liver and spleen are enlarged. Seven types of Farber disease have been described, each with slightly different characteristics. Types 4 and 5 are generally associated with severe neurological problems.^[1]

Last updated: 6/15/2020

This table lists symptoms that people with this disease may have. For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed. This information comes from a database called the Human Phenotype Ontology (HPO) . The HPO collects information on symptoms that have been described in medical resources. The HPO is updated regularly. Use the HPO ID to access more in-depth information about a symptom.

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Medical Terms	Other Names	Learn More: HPO ID
80%-99% of people have these symptoms
Arthritis	Joint inflammation	0001369
Flexion contracture	Flexed joint that cannot be straightened	0001371
Joint swelling		0001386
Periarticular subcutaneous nodules		0007470
30%-79% of people have these symptoms
Arthralgia	Joint pain	0002829
Cherry red spot of the macula		0010729
EMG: chronic denervation signs		0003444
Failure to thrive	Faltering weight Weight faltering [ more ]	0001508
Foam cells in visceral organs and CNS		0003640
Global developmental delay		0001263
Hoarse cry		0001615
Infantile muscular hypotonia	Decreased muscle tone in infant	0008947
Intellectual disability	Mental deficiency Mental retardation Mental retardation, nonspecific Mental-retardation [ more ]	0001249
5%-29% of people have these symptoms
Abnormal conjunctiva morphology		0000502
Abnormal epiglottis morphology		0005483
Abnormal sternum morphology	Abnormality of the sternum Sternal anomalies [ more ]	0000766
Abnormality of the elbow	Abnormality of the elbows	0009811
Abnormality of the knee		0002815
Abnormality of the wrist	Abnormalities of the wrists	0003019
Atelectasis	Partial or complete collapse of part or entire lung	0100750
Brain atrophy	Brain degeneration Brain wasting [ more ]	0012444
Developmental regression	Loss of developmental milestones Mental deterioration in childhood [ more ]	0002376
Diffuse reticular or finely nodular infiltrations		0002207
Dysphonia	Inability to produce voice sounds	0001618
Feeding difficulties	Feeding problems Poor feeding [ more ]	0011968
Hepatosplenomegaly	Enlarged liver and spleen	0001433
Laryngeal stridor		0006511
Macular degeneration		0000608
Mutism	Inability to speak Muteness [ more ]	0002300
Myoclonus		0001336
Nodular pattern on pulmonary HRCT		0025392
Osteoporosis		0000939
Recurrent fever	Episodic fever Increased body temperature, episodic Intermittent fever [ more ]	0001954
Recurrent upper respiratory tract infections	Recurrent colds	0002788
Respiratory distress	Breathing difficulties Difficulty breathing [ more ]	0002098
Respiratory insufficiency	Respiratory impairment	0002093
Short stature	Decreased body height Small stature [ more ]	0004322
Skeletal muscle atrophy	Muscle degeneration Muscle wasting [ more ]	0003202
Spasticity	Involuntary muscle stiffness, contraction, or spasm	0001257
Visual fixation instability		0025405
Weak cry		0001612
1%-4% of people have these symptoms
Abnormal facial shape	Unusual facial appearance	0001999
Anemia	Low number of red blood cells or hemoglobin	0001903
Ascites	Accumulation of fluid in the abdomen	0001541
Chronic diarrhea		0002028
Elevated hepatic transaminase	High liver enzymes	0002910
Hepatic failure	Liver failure	0001399
Hepatic fibrosis		0001395
Hydrops fetalis		0001789
Infantile spasms		0012469
Intrahepatic cholestasis with episodic jaundice		0006575
Loss of voice		0001686
Lymphadenopathy	Swollen lymph nodes	0002716
Nystagmus	Involuntary, rapid, rhythmic eye movements	0000639
Opacification of the corneal stroma		0007759
Paraparesis	Partial paralysis of legs	0002385
Short finger	Stubby finger	0009381
Short toe	Short toes Stubby toes [ more ]	0001831
Thrombocytopenia	Low platelet count	0001873
Percent of people who have these symptoms is not available through HPO
Autosomal recessive inheritance		0000007
Hepatomegaly	Enlarged liver	0002240
Irritability	Irritable	0000737
Lipogranulomatosis		0040139
Motor delay		0001270
Progressive	Worsens with time	0003676
Splenomegaly	Increased spleen size	0001744
Variable expressivity		0003828

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Do you have more information about symptoms of this disease? We want to hear from you.

Last updated: 12/1/2020

Cause Cause

Farber disease occurs when the ASAH1 gene is not working correctly. DNA changes known as pathogenic variants are responsible for making genes work incorrectly or sometimes, not at all.^[2]

Last updated: 6/15/2020

Inheritance Inheritance

Farber disease is inherited in an autosomal recessive pattern.^[2] All individuals inherit two copies of each gene. Autosomal means the gene is found on one of the numbered chromosomes found in both sexes. Recessive means that both copies of the responsible gene must be altered to have the condition.

People with autosomal recessive conditions inherit one alteration from each of their parents. The parents, who each have one gene alteration, are known as carriers. Carriers of an autosomal recessive condition typically do not have any signs or symptoms (they are unaffected). When two carriers of an autosomal recessive condition have children, there is a 25% (1 in 4) chance to have a child with the condition.

Last updated: 6/15/2020

Diagnosis Diagnosis

Farber disease is diagnosed through a clinical history and exam and specialized tests looking for abnormalities in white blood cells. Genetic testing may also be used to confirm the diagnosis.^[2]^[4]

Last updated: 6/15/2020

Testing Resources

The Genetic Testing Registry (GTR) provides information about the genetic tests for this condition. The intended audience for the GTR is health care providers and researchers. Patients and consumers with specific questions about a genetic test should contact a health care provider or a genetics professional.
Orphanet lists international laboratories offering diagnostic testing for this condition.

Treatment Treatment

Treatment for Farber disease is focused on managing the symptoms. Corticosteroids can be given to help with pain. Individuals with difficulty breathing due to swelling and abnormal fat build-up in the upper airway may require a breathing tube (tracheostomy). In some cases, surgery or a bone marrow transplant may be helpful.^[1]^[3]

Specialists involved in the care of someone with Farber disease may include:

Medical geneticist
Neurologist
Rheumatologist
Pain management specialist
Otolaryngologist (ENT)

Last updated: 6/15/2020

Statistics Statistics

Farber disease is very rare. Less than 200 people with Farber disease have been described in the medical literature. The exact number of people with this condition is unknown.^[2]

Last updated: 6/15/2020

Do you have updated information on this disease? We want to hear from you.

Find a Specialist Find a Specialist

If you need medical advice, you can look for doctors or other healthcare professionals who have experience with this disease. You may find these specialists through advocacy organizations, clinical trials, or articles published in medical journals. You may also want to contact a university or tertiary medical center in your area, because these centers tend to see more complex cases and have the latest technology and treatments.

If you can’t find a specialist in your local area, try contacting national or international specialists. They may be able to refer you to someone they know through conferences or research efforts. Some specialists may be willing to consult with you or your local doctors over the phone or by email if you can't travel to them for care.

You can find more tips in our guide, How to Find a Disease Specialist. We also encourage you to explore the rest of this page to find resources that can help you find specialists.

Healthcare Resources

To find a medical professional who specializes in genetics, you can ask your doctor for a referral or you can search for one yourself. Online directories are provided by the American College of Medical Genetics and the National Society of Genetic Counselors. If you need additional help, contact a GARD Information Specialist. You can also learn more about genetic consultations from Genetics Home Reference.

Related Diseases Related Diseases

Related diseases are conditions that have similar signs and symptoms. A health care provider may consider these conditions in the table below when making a diagnosis. Please note that the table may not include all the possible conditions related to this disease.

Conditions with similar signs and symptoms from Orphanet
Differential diagnoses include juvenile idiopathic arthritis, stiff skin syndrome and lethal restrictive dermopathy. Encephalopathy due to prosaposin deficiency should also be excluded. Visit the Orphanet disease page for more information.

Research Research

Research helps us better understand diseases and can lead to advances in diagnosis and treatment. This section provides resources to help you learn about medical research and ways to get involved.

Clinical Research Resources

Orphanet lists European clinical trials, research studies, and patient registries enrolling people with this condition.

Living With Living With

Living with a genetic or rare disease can impact the daily lives of patients and families. These resources can help families navigate various aspects of living with a rare disease.

Financial Resources

The Social Security Administration has included this condition in their Compassionate Allowances Initiative. This initiative speeds up the processing of disability claims for applicants with certain medical conditions that cause severe disability. More information about Compassionate Allowances and applying for Social Security disability is available online.

Learn More Learn More

These resources provide more information about this condition or associated symptoms. The in-depth resources contain medical and scientific language that may be hard to understand. You may want to review these resources with a medical professional.

Where to Start

The American Society of Gene & Cell Therapy provides information on the treatment of genetic diseases.
Genetics Home Reference (GHR) contains information on Farber disease. This website is maintained by the National Library of Medicine.
The National Institute of Neurological Disorders and Stroke (NINDS) collects and disseminates research information related to neurological disorders. Click on the link to view information on this topic.
The National Organization for Rare Disorders (NORD) has a report for patients and families about this condition. NORD is a patient advocacy organization for individuals with rare diseases and the organizations that serve them.

In-Depth Information

The Monarch Initiative brings together data about this condition from humans and other species to help physicians and biomedical researchers. Monarch’s tools are designed to make it easier to compare the signs and symptoms (phenotypes) of different diseases and discover common features. This initiative is a collaboration between several academic institutions across the world and is funded by the National Institutes of Health. Visit the website to explore the biology of this condition.
Online Mendelian Inheritance in Man (OMIM) is a catalog of human genes and genetic disorders. Each entry has a summary of related medical articles. It is meant for health care professionals and researchers. OMIM is maintained by Johns Hopkins University School of Medicine.
Orphanet is a European reference portal for information on rare diseases and orphan drugs. Access to this database is free of charge.
PubMed is a searchable database of medical literature and lists journal articles that discuss Farber disease. Click on the link to view a sample search on this topic.

News & Events News & Events

News

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December 1, 2020
Rare Diseases Are Not Rare - Gallery of Creative Work Raises Awareness of Rare Diseases
September 1, 2020
NIH-Supported Research Survey to Examine Impact of COVID-19 on Rare Diseases Community
May 22, 2020
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May 21, 2020

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Have a question? Contact a GARD Information Specialist.

References References

Zielonka M, arbade SF, Kölker S, Hoffmann GF, Ries M. A cross-sectional quantitative analysis of the natural history of Farber disease: an ultra-orphan condition with rheumatologic and neurological cardinal disease features. Genet Med. 2018; 20(5):524-530. https://pubmed.ncbi.nlm.nih.gov/29048419.
Yu FPS, Amintas S, Levade T, Medin JA. Acid ceramidase deficiency: Farber disease and SMA-PME. Orphanet J Rare Dis. 2018; 13(1):121. https://pubmed.ncbi.nlm.nih.gov/30029679.
Ehlert K, Levade T, Di Rocco M, et al. Allogeneic hematopoietic cell transplantation in Farber disease. J Inherit Metab Dis. 2019; 42(2):286-294. https://pubmed.ncbi.nlm.nih.gov/30815900.
Schuchman EH. Acid ceramidase and the treatment of ceramide diseases: The expanding role of enzyme replacement therapy. Biochim Biophys Acta. 2016; 1862(9):1469-1471. https://pubmed.ncbi.nlm.nih.gov/27155573.