Ultrastructural and histochemical studies of bioptic and postmortem tissue samples from ten Fabry hemizygotes showed lysosomal storage in adipocytes as a constant feature of the classic phenotype of α-galactosidase (GLA) deficiency. The storage was represented by a crescent-shaped line of storage lysosomes of varying thicknesses restricted to the perinuclear subplasmalemmal area. The ultrastructure of the storage lysosomes was dominated by concentric lipid membranes modified by simultaneous deposition of autofluorescent ceroid. Storage was widely expressed in adipose tissue. The number of storage lysosomes was increased, and the lysosomes were more clustered in adipocytes with less voluminous lipid content. The findings should attract interest to studies of adipose tissue biology in Fabry disease, a topic that has not been studied so far. In terms of cell biology, the observations represent indirect evidence of significant lysosomal turnover of α-galactose lipid conjugates in adipocytes demasked by GLA deficiency. The results extend the thus far limited information on the adipocyte lysosomal system and its participation in lysosomal storage disorders.

• MeSH
• alpha-Galactosidase genetics   metabolism   MeSH
• Biopsy MeSH
• Fabry Disease enzymology   genetics   pathology   MeSH
• Phenotype MeSH
• Genetic Predisposition to Disease MeSH
• Glycogen metabolism   MeSH
• Hemizygote MeSH
• Humans MeSH
• Lysosomes enzymology   ultrastructure   MeSH
• Mutation MeSH
• Autopsy MeSH
• Adipocytes enzymology   ultrastructure   MeSH
• Check Tag
• Humans MeSH
• Male MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Names of Substances
• alpha-Galactosidase MeSH
• Glycogen MeSH

We report a female patient with Gaucher disease (GD) type I on ERT (imiglucerase) for 5 years, which led to a significant general improvement. Aged 59 years she underwent an episode of altitude sickness followed by sepsis, disseminated intravascular coagulation, and multiorgan failure. She succumbed to a cerebral haemorrhage. Autopsy revealed liver cholestatic cirrhosis and multifocal liver carcinoma with immunophenotype compatible with cholangiocarcinoma. Analysis of the storage process revealed its absence or very low levels in the majority of liver and spleen macrophages. Gaucher cells (GCs) were seen only as occasional aggregates of various sizes in these organs. GCs were seen also in the leptomeninx of the cerebellum and as infrequent perivascular clusters in both the grey and white cerebral matters. Bone marrow was heavily infiltrated with GCs, especially in the adipocyte-rich part. GCs in this location displayed varied degrees of cytoplasmic vacuolation unrelated to the lysosomal compartment, caused by droplets of triglyceride, and interpreted as due to resorption of fragments of altered white adipocytes. All these observations point to the relative efficacy of ERT in covering the standard substrate load, which should not be exceeded as it would lead to the evolution of mature GCs. The results are discussed in relation to our recently published hypothesis on GD cell pathology.

• MeSH
• Biological Transport, Active physiology   MeSH
• Gaucher Disease drug therapy   metabolism   pathology   MeSH
• Glucosylceramidase therapeutic use   MeSH
• Middle Aged MeSH
• Humans MeSH
• Autopsy MeSH
• Recombinant Proteins therapeutic use   MeSH
• Check Tag
• Middle Aged MeSH
• Humans MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Case Reports MeSH
• Research Support, Non-U.S. Gov't MeSH
• Names of Substances
• Glucosylceramidase MeSH
• imiglucerase MeSH Browser
• Recombinant Proteins MeSH