Sign Up for a Free Account
  • Updated 01.06.2020
  • Released 04.21.1995
  • Expires For CME 01.06.2023

Farber disease

Introduction

This article includes discussion of Farber disease, acid ceramidase deficiency, disseminated lipogranulomatosis, Farbers disease, Farber’s disease, Farber lipogranulomatosis, and Farber Uzman syndrome. The foregoing terms may include synonyms, similar disorders, variations in usage, and abbreviations.

Overview

Farber disease is an autosomal recessive progressive devastating disease of lipid metabolism associated with deficiency of lysosomal acid ceramidase 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 may exist, including a form of spinal muscular atrophy associated with progressive myoclonic epilepsy. Hematopoietic stem cell transplantation is effective for the nonneurologic aspects of the disease. Enzyme replacement therapy for this disease is being developed.

Key points

• Farber disease is a rare multisystemic autosomal recessive disease.

• Unique plasma biomarkers may help in diagnosis and 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 Dr. Sidney Farber in 1957, in the Journal of the Mount Sinai Hospital, as part of a Festschrift for Paul Klemperer (21). Sidney Farber considered it of special interest because "it (is) a possible bridge between what had appeared to be 2 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.

The "true" genetic component was represented by neuronal storage material that was thought to contain lipids, carbohydrates, and protein, whereas the inflammatory component, resembling histiocytosis-x, was evidenced by granulomatous inflammatory lesions in skin, joints, and larynx. Subsequent studies have shown, however, that a genetically determined abnormality accounts for all of the features of Farber lipogranulomatosis. In 1967, Prensky and associates showed that the tissues of Farber disease patients contained abnormally high levels of ceramide (50), and it was shown later that the ceramide accumulation accounted both for the neuronal storage and the inflammatory component (45). In 1972, Sugita and associates demonstrated that the ceramide accumulation was due to a deficiency of acid ceramidase (61), and Farber disease is now classified as 1 of the lysosomal storage disorders. Acid ceramidase was purified in 1995 (07) and cloned in 1996 (33). A mutation of this gene was identified in 1 patient with Farber disease (33).

This is an article preview.
Start a Free Account
to access the full version.

  • Nearly 3,000 illustrations, 
including video clips of 
neurologic disorders.

  • Every article is reviewed by our esteemed Editorial Board for accuracy and currency.

  • Full spectrum of 
neurology in 1,200 
comprehensive articles.

Questions or Comment?

MedLink, LLC

10393 San Diego Mission Rd, Suite 120

San Diego, CA 92108-2134

Toll Free (U.S. + Canada): 800-452-2400

US Number: +1-619-640-4660

Support: service@medlink.com

Editor: editor@medlink.com