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  • Updated 06.24.2022
  • Released 04.21.1995
  • Expires For CME 06.24.2025

Farber disease

Introduction

Overview

Farber disease is an autosomal recessive, progressive, devastating disease of lipid metabolism associated with deficiency of lysosomal acid ceramidase, which is caused by ASAH1 gene mutations leading to accumulation of ceramide in cells. The disease presents most commonly during the first few months after birth with painful and progressively deformed joints, subcutaneous nodules (particularly near joints and over pressure points), and progressive hoarseness due to laryngeal involvement. The nervous system is often involved. Other forms include a rare type of spinal muscular atrophy associated with progressive myoclonic epilepsy. Hematopoietic stem cell transplantation is effective for the non-neurologic aspects of the disease.

Key points

• Farber disease is a rare multisystemic autosomal recessive disease.

• Unique plasma biomarkers may help in diagnosis and in assessing specific therapy.

• Progressive hoarseness is a clinical hallmark.

• A form with high residual acid ceramidase activity associated with spinal muscular atrophy and progressive myoclonic epilepsy has been described.

• Moderate Farber disease is a subset of juvenile idiopathic arthritis.

Historical note and terminology

The first patient with Farber lipogranulomatosis was described by American pediatric pathologist Sidney Farber (1903-1973) in 1957, in the Journal of the Mount Sinai Hospital, as part of a Festschrift for Paul Klemperer (27).

American pediatric pathologist Sidney Farber MD (1903-1973)

Dr. Sidney Farber MD was the founder of Children's Hospital Cancer Research Foundation in the 1950s and 1960s. The Photograph was taken in 1960 for the National Cancer Institute of the US National Institutes of Health. In 1957,...

Farber considered it of special interest because "it (is) a possible bridge between what had appeared to be two etiologically unrelated groups of disorders, namely the ‘true’ (genetically determined) metabolic disorders, such as Niemann-Pick disease, and the (nongenetic) inflammatory histiocytoses, such as Letterer-Siwe disease or histiocytosis-x.”

Subsequent studies have shown that a genetically determined abnormality accounts for all of the features of Farber lipogranulomatosis. In 1967, American pediatric neurologist Arthur L Prensky (1930-) and associates showed that the postmortem tissues of a patient with Farber disease contained abnormally high levels of ceramide (65). Swiss-American neurogeneticist Hugo Moser (1924-2007) then demonstrated that the ceramide accumulation accounts for both the neuronal storage and the inflammatory component (58). In 1972, Mutsumi Sugita and associates, including Hugo Moser, working at the Eunice Kennedy Shriver Center in Massachusetts, demonstrated that the ceramide accumulation was due to a deficiency of acid ceramidase (78).

Farber disease is now classified as a lysosomal storage disorder. Acid ceramidase was purified in 1995 (10) and cloned in 1996 (42). In 1996, a mutation of this gene was identified in a patient with Farber disease (42).

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