Ceramidase, deficiency

Sugita, M., Dulaney, J.T., Moser, H.W., 1972, Ceramidase deficiency in Farber s disease (hpogranulomatosis). Science 178 1100-1102. 

Ceramides are broken down by the enzyme ceramidase. Deficiency of ceramidase leads to accumulation of ceramides, which results in deformed joints and problems with heart, lungs, and lymph nodes. The syndrome is usually fatal within a few years of birth. 

Burek, C., Roth, J., Koch, H. G., Harzer, K., Los, M., and Schulze-Osthoff, K. (2001). The role of ceramide in receptor- and stress-induced apoptosis studied in acidic ceramidase-deficient Farber disease cells. Oncogene 45, 6493-6502. 

Farber disease Acid ceramidase deficiency Sugita et at., 1972... 

Farber s disease is a rare disorder caused by deficiency of acid ceramidase and is associated with the accumulation of ceramide in subcutaneous tissues, joints, kidney, lung and neurons. Gangliosides also accumulate. 

A nonlysosomal ceramidase in some tissues functions optimally at neutral or alkaline pH and participates in the synthesis and breakdown of ceramide. Deficiency of lysosomal (acid) ceramidase in Farber s disease (lipogranu-lomatosis) causes accumulation of ceramide. The disease is inherited as an autosomal recessive trait and is characterized by granulomatous lesions in the skin, joints, and larynx and moderate nervous system dysfunction it may also involve heart, lungs, and lymph nodes. It is usually fatal during the first few years of life. 

J.Norris and collaborators showed that also acid ceramidase activity in cells vanishes following treatment with desipramine (Elojeimy et ah, 2006) thus, the compound depletes lysosomes of both a ceramide generating and consuming enzyme (and few authors have studies the net effect on cellular ceramide levels when using such inhibitors). Therefore, the many studies in the literature using this class of ASMase inhibitors have to be taken with caution firm conclusions can only be reached when effects seen with these compounds are backed up by experiments with genetically ASMase deficient cells or cells depleted for ASMase by using siRNA. 

Both human and canine globoid cell leukodystrophy are caused by deficiencies in jS-D-galactosyl-ceramidase and -sphingosidase, although different mutations underlie the enzymic defects. ... 

Two enzymatic defects have been discovered in GLD, and additional ones have to be postulated to explain all the observations. The imbalance between cerebrosides and sulphatides is explicable by a defect of the cerebroside-sulphotransferase [43, 44, 45], an enzyme first demonstrated in animals [46] where adenosine-3 -phosphate 5 -sulphato-phosphate serves as sulphate donor. This enzymatic deficiency is noted also in the kidneys of these patients [43]. Other enzymes such as acid phosphatase, sulphatase and other sphingolipid hydrolases, including ceramidase [45], however, show normal activity [25]. 

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