Homozygous N396T mutation in Gaucher disease: Portuguese sisters with markedly different phenotypes

Samantha Kimball^1,2, Francis Choy⁴, Agnes Zay⁵, Dominick Amato^3
1Department of Nutritional Sciences, University of Toronto, Canada; ²Department of Laboratory Medicine and Pathology, ³Department of Medicine, Division of Hematology, Mt Sinai Hospital, Toronto, Canada; ⁴Department of Biology, University of Victoria, Victoria, Canada; ⁵MRC Center for Regenerative Medicine, University of Edinburgh, Edinburgh, Scotland

Abstract: Gaucher disease (GD) is characterized by reduced activity of glucocerebrosidase leading to complications in the reticuloendothelial system. N396T, a rarer mutation of the glucocerebrosidase gene, has been encountered in Portuguese populations and has generally been associated with milder phenotypes. This report presents brief histories of two Portuguese sisters, both with homozygous N396T mutations. These patients are phenotypically very different despite the fact that in both patients residual enzyme activity is very low. The case of patient 1 is complicated by comorbid diabetes mellitus and human immunodeficiency virus (HIV) infection. Enzyme replacement therapy (ERT) improved this patient's clinical picture sufficiently to enable antiretroviral treatment to proceed for the HIV. This report demonstrates the poor correlation of clinical GD with genotype as well as with residual enzyme activity. It further illustrates how treatment of the underlying GD with ERT improved symptoms allowing for antiretroviral therapy thereby improving both the GD and HIV.

Keywords: Gaucher disease, N396T mutation, glucocerebrosidase, HIV