Guidance on the use of miglustat for treating patients with type 1 Gaucher disease.

Type 1 Gaucher disease (GD) is a progressive lysosomal storage disorder due to an autosomal recessive deficiency of glucocerebrosidase. Clinical manifestations include anemia, thrombocytopenia, hepatosplenomegaly, and bone and pulmonary disease. Intravenous enzyme replacement (ERT) with imiglucerase is the accepted standard for treatment of symptomatic patients.

Radiological evidence of early cerebral microvascular disease in young children with Fabry disease.

We report on 2 children with Fabry disease who had radiologic evidence of microvascular central nervous system involvement despite the clinical absence of renal, cardiac, or cerebral manifestations. This suggests that treatment with enzyme replacement therapy may be necessary early in the disease to avoid irreversible complications.

Correlation of surrogate markers of Gaucher disease. Implications for long-term follow up of enzyme replacement therapy.

Background: The excessive storage of cellular debris in the lysosomal storage disorders triggers a variety of cellular responses. Some of these responses are maladaptative and result in the pathology of these diseases. To some extent, cellular responses are specific to the stored material, which influences the pathophysiology of the disease and results in some of its characteristic features.

Fabry disease in genetic counseling practice: recommendations of the National Society of Genetic Counselors.

The objective of this document is to provide health care professionals with recommendations for genetic counseling and testing of individuals with a suspected or confirmed diagnosis of Fabry disease, with a family history of Fabry disease, and those identified as female carriers of Fabry disease. These recommendations are the opinions of a multicenter working group of genetic counselors, medical geneticists, and other health professionals with expertise in Fabry disease counseling, as well as an individual with Fabry disease who is a founder of a Fabry disease patient advocacy group in the United States. The recommendations are U.

Gene therapy for the lysosomal storage disorders.

The lysosomal storage disorders (LSD) are monogenic inborn errors of metabolism with heterogeneous pathophysiology and clinical manifestations. In recent decades, these disorders have been models for the development of molecular and cellular therapies for inherited metabolic diseases. Studies in preclinical in vitro systems and animal models have established proof-of-concept for the development of bone marrow transplantation (BMT) and enzyme-replacement therapy (ERT) as therapeutic options for several LSDs.

Demonstration of feasibility of in vivo gene therapy for Gaucher disease using a chemically induced mouse model.

Progress towards developing gene therapy for Gaucher disease has been hindered by the lack of an animal model. Here we describe a mouse model of Gaucher disease which has a chemically induced deficiency of glucocerebrosidase and that accumulates elevated levels of glucosylceramide (GL-1) in the lysosomes of Kupffer cells. Administration of mannose-terminated glucocerebrosidase (Cerezyme) resulted in the reduction of GL-1 levels in the livers of these animals.