Morbus Farber: eine Ursache der Arthritis im Kindesalter

Zusammenfassung

Morbus Farber ist eine Erkrankung des Sphingolipid-Metabolismus, der seine Ursache in einem Mangel des lysosomalen Enzyms saure Ceramidase hat, woraus eine Unfähigkeit der Zellen entsteht, Ceramide zu zerlegen. Die Erkrankung tritt als Folge der Vererbung von Mutationen auf beiden Allelen des ASAH1-Gens auf, und zeigt sich hauptsächlich mit einem für lysosomale Speichererkrankungen untypischen, entzündlichen Phänotyp. Betroffen sind Gelenke und Bindegewebe. Eine typische Fazies, Dysostose oder wesentliche Organomegalie fehlen. Dies begründet sich in der Tatsache, dass Ceramid ein pro-inflammatorisches und pro-apoptotisches Sphingolipid ist. Diese Eigenschaften sind offensichtlich hauptsächlich verantwortlich für das klinische Erscheinungsbild der Erkrankung, d. h.: Gelenkbeteiligung in Form von Kontrakturen und/oder Arthritis, subkutane Noduli und eine laryngeale Mitbeteiligung in Form einer heiseren oder schwachen Stimme. In den letzten Jahren hat sich jedoch gezeigt, dass Manifestation, Phänotyp und Verlauf des M. Farber eine starke Variabilität aufweisen: von Tod innerhalb weniger Monate nach der Geburt bis zu einem abgeschwächten Verlauf mit Diagnosestellung im jungen Erwachsenenalter. Es ist bemerkenswert, dass manche Patienten mit Morbus Farber auf eine Behandlung mit anti-entzündlichen Medikamenten – insbesondere mit Biologika – gegen TNF-alpha oder Interleukin-6-Rezeptoren, mit einer Schmerzreduktion und einer Verbesserung der Schwere der Arthritis reagiert haben. Es ist daher angebracht, einen Test auf Morbus Farber bei Patienten in Betracht zu ziehen, deren Arthritis nicht adäquat auf eine Behandlung anspricht.

Abstract

Farber disease is a disorder of sphingolipid metabolism, resulting from deficiency in the lysosomal enzyme acid ceramidase and the inability of cells to break down ceramide. The disease occurs when deleterious mutations are inherited in both alleles of the ASAH1 gene. What is unusual for a lysosomal storage disease is that it principally presents with an inflammatory phenotype affecting joints and connective tissue, without typical facies, dysostosis or significant organomegaly. This is because ceramide is a pro-inflammatory and pro-apoptotic sphingolipid, and these properties appear to be primarily responsible for the major clinical features of the disease, which are: joint disease in the form of contractures and/or arthritis with synovitis, subcutaneous nodules, and laryngeal involvement presenting as a hoarse or weak voice. In recent years, it has become clear that the presentation, phenotype, and outcome of the disease is widely variable, ranging from death within months of birth to an attenuated course with normal achievement of physical and intellectual developmental milestones but with progressive arthritis and joint deformation, along with a hoarse voice and subcutaneous nodules. In this context, the current view of the Farber phenotype of acid ceramidase deficiency is rather that of a spectrum reaching from severe disease leading to death in early childhood, to mild disease with patients living well into adulthood. It is important to note that some Farber patients have shown a response to treatment with anti-inflammatory medications, particularly with biologicals, including a reduction in pain and limited decrease in the severity of arthritis. Therefore, it is justified to consider testing for Farber disease in certain patients with arthritis in childhood who have not responded adequately to standard of care treatment.

Schlüsselwörter

Farber - KontrakurenArthritisNoduli - Kindesalter

Key words

Farbercontracture - arthritis - - nodule - children

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