Fabry-Gen-Phen: The Fabry Working Group Genotype Phenotype Database

The Fabry Working Group Genotype-Phenotype Database (Fabry-Gen-Phen database) is a database designed to provide reliable information on genotype-phenotype associations in Fabry disease.

The data currently included in the Fabry-Gen-Phen database stem from 3 European centers of excellence (Amsterdam UMC, location AMC, the Netherlands; Royal Free London NHS Foundation Trust, United Kingdom and University Hospital Wuerzburg, Germany) combined with data from the Canadian Fabry Disease Initiative Database (CFDI). The phenotype of all patients (N=669) included in this database has been defined using citeria outlined below (and in the flow-chart), allowing strict categorization according to the extent of current knowledge and insight.

For a given GLA variant the Fabry-Gen-Phen database will display the following parameters:

-the number of male and female patients with a classical or a non-classical phenotype or the number of individuals without Fabry disease (benign variant),

-the GLA enzyme activity in leucocytes of these patients/individuals (median and range) in nmol/mg protein

-plasma lysoGb3 level (median and range) in nmol/l.

This enables the user to determine if a given GLA variant is associated with FD and if so, with which phenotype. For most variants a clear phenotypic distinction can be provided, however, for a limited number of variants the database may show both patients classified as having a classical phenotype as well as patients classified as having a non-classical phenotype. This most likely represents the continuous spectrum of the disease, which does not always fully fit in a dichotomous disease classification.

The original database was established as part of the thesis studies of dr. M. Arends to support the appropriate use of agalsidase alfa and beta. It included not only the above mentioned parameters, but additional clinical and biochemical aspects. This database has been used for the studies described in the following publications:

• Arends et al, J Inherit Metab Dis 2018
• Arends et al, J Am Soc Nephrol 2017
• Arends et al, PloS One 2017
• Arends et al, J Med Genet 2018
• Arends et al, Mol Genet Metab 2017

Fabry-Gen-Phen user manual

The search field can be used to search for a GLA variant. The variant can be entered in the search field at protein level (e.g. p.Ala309Pro or A309P (short)) or at the DNA level (e.g. c.925G>C or IVS4+1G>A or c.639+1G>A). The search result will show the number of patients in the database per phenotypical group, divided by gender with this variant, their phenotype, enzyme activity and lysoGb3 level.

NB the database does not function properly in Internet Explorer, please use Google Chrome, Firefox or Safari.