Skin lipid abnormalities in Gaucher's disease

In the epidermis of terrestrial vertebrates stratum corneum lipids are known to play an important role as regulators of skin permeability; particularly ceramides, some of which with very long chain, hydroxy fatty acids, are important components of this "barrier" function. Ceramides are derived from the hydrolysis of previous existing glucosylceramide during the terminal stages of epidermal differentiation, due to the presence of a lisosomal-like glucosylceramidase localised in the lamellar bodies in the space between stratum granulosum and the inferior layer of stratum corrieum: the deficiency of glucosylceramidase, localized in lysosome, is responsible of Gaucher's disease. In this study we investigated the glycolipids and ceramide distribution in the epidermis of 4 Gaucher's patients (two of type 1 and two of type 3). compaired with the same parameters in 4 healthy donors. The comparison between the pathological samples and the healthy ones, indicates an impairment of the degradation of glucosylceramide to ceramide in the lamellar bodies of Gaucher's patients stratum corneum, as shown by the high percentage of the former (range: 48-69% of the total glycolipids), and the complete absence of the latter. We are now evaluating the usefulness of topical therapy (in addition to the replacement therapy with Ceradase) with the use of a lotion containing commercially available 3 hydroxy ceramide, which fatty acids composition is closely related to that of the main ceramide present in human skin.