Farber Syndrome

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Classification according to ICD-10
E75.2 Other sphingolipidoses (including Farber's disease)
ICD-10 online (WHO version 2019)

The Farber disease , even Farber's disease , Crohn's Farber , ceramidase deficiency or disseminated Lipogranulomatose called, is an extremely rare genetically related lysosomal storage disease ( Thesaurismose ).

Genetics and Etiology

Farber syndrome is inherited as an autosomal - recessive trait. The affected ASAH gene is located on chromosome 8 gene locus p22-p21.3. It codes for the enzyme acid ceramidase (N-acylsphingosine amidohydroxylase = ASAH). The ASAH gene is 30 kb in length and contains 14 exons . In most cases, point mutations in the ASAH gene lead to Farber's syndrome.

The mutations cause a lack of activity of the acid ceramidase. Acid ceramidase is an enzyme of the lysosomal hydrolase type , which catalyzes the cleavage of ceramides into sphingosine and fatty acids . The lack of activity of the enzyme caused by the genetic defect leads to intracellular storage of ceramide.

The disease can manifest itself very differently depending on the patient and the degree of lack of activity. The symptoms typical of Farber's syndrome can appear as early as infancy or even after puberty.

Symptoms and diagnosis

The clinical course of Farber's syndrome can vary greatly. The most common symptoms in affected patients are contractures of the joints , periarticular subcutaneous nodules, short stature (hyposomy), abnormalities of the larynx ( laryngomalacia ) and corneal opacity . Occasionally, an enlargement of the liver and spleen is observed ( hepatosplenomegaly ).

The diagnosis can be made quickly and reliably - even prenatally - by measuring the ceramidase activity.

therapy

An effective, curative therapy is currently not possible. Treatment is usually symptomatic with pain relievers and corticosteroids . Plastic surgery can also be used for severe deformations .

Initial description

Farber's syndrome was first described in 1952 by the American pathologist Sidney Farber (1903-1973). He is the namesake for the disease.

Individual evidence

  1. ↑ CM Li et al: The human acid ceramidase gene (ASAH): structure, chromosomal location, mutation analysis and expression. In: Genomics 62, 1999, pp. 223-231. PMID 10610716
  2. ↑ J. Bar et al .: Molecular analysis of acid ceramidase deficiency in patients with Farber disease. In: Hum. Mutat. 17, 2001, pp. 199-209. PMID 11241842
  3. ↑ AH Fensom et al: Prenatal diagnosis of Farber's disease. In: Lancet II 1979, pp. 990-992.
  4. ↑ S. Farber: A lipid metabolic disorder: disseminated lipogranulomatosis; a syndrome with similarity to, and important difference from, Niemann-Pick and Hand-Schüller-Christian disease. In: American Journal of Diseases of Children 84, 1952, pp. 499-500. PMID 12975849

literature

  • M. Sugita et al .: Ceramidase deficiency in Farber's disease (lipogranulomatosis). In: Science 178, 1972, pp. 1100-1102. PMID 4678225
  • GH Amirhakimi et al .: Familial lipogranulomatosis (Faber's disease). In: Clin. Genet. 9, 1976, pp. 625-630, PMID 1277575
  • SE Antonarakis et al: Phenotypic variability in siblings with Farber disease. In: J. Pediat. 104, 1984, pp. 406-409. PMID 6423791
  • Y. Ben-Yoseph et al: Leukocyte and plasma N-laurylsphingosine deacylase (ceramidase) in Farber disease. In: Clin. Genet. 36, 1989, pp. 38-42. PMID 2504515
  • J. Clausen and S. Rampini: Chemical studies of Farber's disease. In: Acta Neurol. Scand. 46, 1970, pp. 313-322. PMID 5535909
  • S. Farber et al: Lipogranulomatosis: a new lipo-glyco-protein 'storage' disease. In: J. Mt. Sinai Hosp. 24, 1957, pp. 816-837.

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