Farber disease (acid ceramidase deficiency)

Farber disease, also called Farber lipogranulomatosis or acid ceramidase deficiency, is a lysosomal storage disorder. Lysosomes are the parts of a cell that break down and recycle used material. When the enzyme acid ceramidase does not work, fats called ceramides build up in cells, especially around the joints and in the lungs, liver and other tissues.

Severity varies widely. Doctors once sorted Farber disease into seven types, but it is now seen as a spectrum of overlapping signs. Some babies become very ill in the first months of life. Others have milder disease that may not be recognized until later childhood or even adulthood.

Farber disease is caused by changes in both copies of the ASAH1 gene, which carries the instructions for acid ceramidase. The enzyme’s activity usually falls below 10 percent of normal.

It is inherited in an autosomal recessive pattern. Each parent usually carries one changed copy and has no symptoms. When both parents are carriers, each pregnancy has a 1 in 4 chance of a child with the condition.

Changes in the same gene can cause a different condition, spinal muscular atrophy with progressive myoclonic epilepsy (SMA-PME), which mainly causes muscle weakness and seizures. That condition is not covered here. Farber disease is not caused by anything a parent did, and a genetic counselor can explain what results mean for the family.

Three classic signs are painful, swollen joints; small lumps of fat under the skin, called nodules or lipogranulomas; and a hoarse voice or weak cry. Signs usually begin in infancy. In a study of 96 published cases, half had their first symptoms by 3 months of age.

Nodules in the throat and airway can make breathing hard, and fat deposits can also affect the lungs and eyes. The liver and spleen may be enlarged, and bones can thin over time.

In severe forms, the brain and spinal cord are affected. Children may have developmental delay, seizures, loss of speech and other skills, or fluid buildup in the brain.

Milder forms are often mistaken for juvenile idiopathic arthritis (JIA), a common type of childhood arthritis. In one group of people with mild or intermediate Farber disease, about 7 in 10 were first diagnosed with JIA.

Farber disease is usually suspected from its three classic signs: lumps under the skin, painful joints and a hoarse voice. Milder forms can be missed when one of these signs is absent, and they are often first diagnosed as juvenile idiopathic arthritis. In babies with severe disease, a large liver and spleen can hide the classic signs.

Confirming it takes lab tests. The most common is an enzyme test on skin cells grown in the lab (fibroblasts), where acid ceramidase activity is usually below 10 percent of normal. White blood cells can also be tested. A genetic test looks for changes in both copies of the ASAH1 gene. A biopsy of a nodule may show fat-filled immune cells.

Testing before or right after birth is usually done only when an older brother or sister has already been diagnosed. In the study of 96 published cases, half were diagnosed by 17 months of age.

There is no cure and no approved medicine for the cause. Care focuses on symptoms: medicines for pain and inflammation, physical therapy to keep joints moving, and sometimes surgery to remove nodules in the hands or mouth. When nodules narrow the airway, some children need a breathing tube placed in the neck (tracheostomy).

A donor stem cell transplant has greatly improved pain and movement in a number of people without brain or nerve involvement. The donor’s white blood cells are thought to supply working enzyme and calm the inflammation. In a 2019 European report of 10 people, the inflammation went away completely in all of them.

Transplant does not seem to protect the brain and nerves. In that report, 4 of the 10 had nervous-system problems before transplant and 6 had them afterward. Two babies transplanted at 9 months of age had better joints and fewer nodules afterward, but their nervous systems still declined.

For these reasons, transplant is mainly considered for people without nervous-system involvement. Farber disease is not named in EBMT’s 2025 transplant indication tables or on NMDP’s list of inherited metabolic disorders. 2026 European guidelines say the benefit of transplant is not established for many rare storage disorders and advise discussion with an expert center.

Other treatments are still in the lab. A lab-made form of the enzyme and gene therapy have helped mice with Farber disease, but neither is approved for people. One UK center reported using tocilizumab, a medicine that blocks an inflammation signal, to ease pain in a child before transplant. It did not stop the nodules from growing.

Pain can be a big part of daily life. Swollen joints and nodules can make it painful to move or use the hands, and young children may be very irritable. Over time, joints can stiffen in bent positions (contractures).

Getting a diagnosis often takes a long time. In the study of 96 published cases, the median delay from first symptoms to diagnosis was about 14 months. Families may see rheumatology and metabolic specialists before the cause is found.

For children without brain involvement, families may weigh a transplant and its risks against years of pain and stiffness. In the 2019 European report, 2 of the 10 people died from transplant complications. When the brain is severely affected, many children do not live past early childhood.

When a transplant is used for Farber disease, the cells come from another person. Published cases have used matched brothers or sisters, other matched relatives, unrelated adult volunteers, a half-matched relative and unrelated cord blood.

In the largest series, 5 of 10 people had a matched unrelated donor. For lysosomal storage disorders, 2026 European guidelines prefer a well-matched unrelated donor who does not carry the gene change over a family donor who does. A 2025 UK report noted that several people with Farber disease have also done well with a matched family donor.

A shortage of registry donors is not the main barrier for this condition. Earlier diagnosis and treatments that reach the brain are the bigger needs. Joining a registry still helps the many other patients who need an unrelated donor.

Farber disease varies a great deal. Babies with the classic severe form often do not live past 2 or 3 years. People without major nervous-system involvement can live much longer; a 2007 review described breathing failure leading to death in the 20s or 30s. Some people with mild forms are not diagnosed until adulthood.

Breathing problems and nervous-system decline are the main threats to life. A donor transplant can clear joint inflammation and nodules, but it does not seem to change nervous-system disease.