Acid ceramidase deficiency: Farber lipogranulomatosis, spinal muscular atrophy associated with progressive myoclonic epilepsy and peripheral osteolysis

Abstract An inherited deficiency of the lysosomal enzyme ceramidase leads to accumulation of the sphingolipid ceramide in several organs such as skin, liver, brain and other tissues, resulting in a broad spectrum of clinical manifestations. The most common form, called Farber lipogranulomatosis, is characterized by subcutaneous skin nodules and a progressive hoarseness, in many cases also the central nervous system is affected. A lethal hydrops fetalis represents the most severe form. A ceramidase deficiency was also found in a few patients in whom neurological symptoms such as spinal muscular atrophy and myoclonus epilepsy dominated the clinical picture, in other adult patients peripheral osteolytic lesions represented the major clinical features. In the ceramidase gene ASAH1, which has been mapped to chromosome 8 and contains 14 exons, more than 60 different mutations have been identified. Presently, no effective treatment is available, but in the future enzyme replacement and gene therapy may become a therapeutic option.