It has recently been emphasised that a subset of patients with type 2 Gaucher disease die in the neonatal period. This report describes an Afghani family with two conceptuses having severe, prenatally detected Gaucher disease. Mutational analysis showed that the family carried a known complex allele which included mutations at amino acids L444P, A456P, and V460V. Although glucocerebrosidase RNA...

Gaucher disease, the most common lysosomal storage disease, is caused by a recessively inherited deficiency in glucocerebrosidase and subsequent accumulation of toxic lipid substrates. Heterozygous mutations in the lysosomal glucocerebrosidase gene (GBA1) have recently been recognized as the highest genetic risk factor for the development of α-synuclein aggregation disorders ("synucleinopathies...

Gaucher disease, the most common type of lysosomal storage disorder, is characterized by an inherited deficiency of the membrane-associated hydrolase, glucocerebrosidase. Glucocerebrosidase catalyzes the hydrolysis of glucocerebroside to ceramide and glucose, a crucial step in the recycling of membrane sphingolipids. The exorbitant cost of the current treatment standard for Gaucher disease, enz...

Gaucher disease is caused by mutations in the glucocerebrosidase gene, which encodes the lysosomal hydrolase glucosylceramidase. Patients with Gaucher disease and heterozygous glucocerebrosidase mutation carriers are at increased risk of developing Parkinson's disease. Indeed, glucocerebrosidase mutations are the most frequent risk factor for Parkinson's disease in the general population. There...

Mutations in the GBA gene that encodes glucocerebrosidase cause the lysosomal storage disorder Gaucher disease but also increase the risk for Parkinson's disease. Mazzulli et al. (2011) uncover a possible mechanism to explain this connection: loss of glucocerebrosidase creates a positive feedback loop of reduced lysosomal function and α-synuclein accumulation, ultimately leading to neurodegener...

In order to increase the delivery to macrophages of p-glucocerebrosidase (the enzyme deficient in macrophages from patients with Gaucher’s disease), we have coupled a synthetic triantennary mannosyl glycopeptide, trimannosyldilysine (Man3Lysz), to the native enzyme. The resulting derivative, Man3Lys2-p-glucocerebrosidase (containing 8 to 9 mol of Man3Lys2/67,000 molecular weight enzyme subunit)...

Several carriers were evaluated for use in the delivery of exogenous glucocerebrosidase to monocytes from Gaucher's disease patients. Only gamma globulin-coated, resealed erythrocytes proved to be an effective vehicle for enzyme delivery. Glucocerebrosidase added in this manner normalized intracellular enzyme levels for at least 18 hr. In this model system for the study of enzyme replacement th...

Gaucher's disease is caused by a deficiency of the lysosomal enzyme glucocerebrosidase (glucosylceramidase; D-glucosyl-N-acylsphingosine glucohydrolase, EC 3.2.1.45); this disorder has been a leading candidate for enzyme replacement trials. A rapid, high-yield method for purification of glucocerebrosidase has been developed. Detergent extraction of human placenta was followed by salt fractionat...