Farber disease

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Disease Profile

Farber disease

<1 / 1 000 000

US Estimated

Europe Estimated

Age of onset

Infancy

ICD-10

E75.2

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.

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

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.

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.

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

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.

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.

Not applicable

Other names (AKA)

Farber lipogranulomatosis; Ceramidase deficiency; Acid ceramidase deficiency;

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

Hepatic fibrosis

Hydrops fetalis

Infantile spasms

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)

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.

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.

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.

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Infancy

E75.2

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

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.

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.

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

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.

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.

Not applicable

Other names (AKA)

Categories

Summary

Symptoms

Cause

Diagnosis

Testing Resources

Treatment

Related diseases

Learn more

Where to Start

In-Depth Information

References

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.

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