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Disease Profile

Farber disease

Prevalence
Prevalence estimates on Rare Medical Network websites are calculated based on data available from numerous sources, including US and European government statistics, the NIH, Orphanet, and published epidemiologic studies. Rare disease population data is recognized to be highly variable, and based on a wide variety of source data and methodologies, so the prevalence data on this site should be assumed to be estimated and cannot be considered to be absolutely correct.
<1 / 1 000 000

< 331

US Estimated

< 514

Europe Estimated

Age of onset

Infancy

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ICD-10

E75.2

Inheritance

Autosomal dominant A pathogenic variant in only one gene copy in each cell is sufficient to cause an autosomal dominant disease

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Autosomal recessive Pathogenic variants in both copies of each gene of the chromosome are needed to cause an autosomal recessive disease and observe the mutant phenotype

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X-linked
dominant X-linked dominant inheritance, sometimes referred to as X-linked dominance, is a mode of genetic inheritance by which a dominant gene is carried on the X chromosome.

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X-linked
recessive Pathogenic variants in both copies of a gene on the X chromosome cause an X-linked recessive disorder

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Mitochondrial or multigenic Mitochondrial genetic disorders can be caused by changes (mutations) in either the mitochondrial DNA or nuclear DNA that lead to dysfunction of the mitochondria and inadequate production of energy.

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Multigenic or multifactor Inheritance involving many factors, of which at least one is genetic but none is of overwhelming importance, as in the causation of a disease by multiple genetic and environmental factors.

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Not applicable

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Other names (AKA)

Farber lipogranulomatosis; Ceramidase deficiency; Acid ceramidase deficiency;

Categories

Congenital and Genetic Diseases; Eye diseases; Metabolic disorders;

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] 

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]

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.

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

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]

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]

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 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)

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

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.

References

  1. 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.
  2. 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.
  3. 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.
  4. 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.

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