Patient centered guidelines for the laboratory diagnosis of Gaucher disease type1

DARDIS A; MICHELAKAKIS H; ROZENFELD PA; FUMIC K; WAGNER JC; PAVAN E; FULLER M; REVEL VILK J; HUGHES D; COX T; AERTS J

ORPHANET JOURNAL OF RARE DISEASES

BIOMED CENTRAL LTD

Lugar: Londres; Año: 2022

1750-1172

Gaucher disease (GD) is an autosomal recessive lysosomal storage disorder due to the defcient activity of the acidbeta-glucosidase (GCase) enzyme, resulting in the progressive lysosomal accumulation of glucosylceramide (GlcCer)and its deacylated derivate, glucosylsphingosine (GlcSph). GCase is encoded by the GBA1 gene, located on chromo‑some 1q21 16 kb upstream from a highly homologous pseudogene. To date, more than 400 GBA1 pathogenic vari‑ants have been reported, many of them derived from recombination events between the gene and the pseudogene.In the last years, the increased access to new technologies has led to an exponential growth in the number of diag‑nostic laboratories ofering GD testing. However, both biochemical and genetic diagnosis of GD are challenging andto date no specifc evidence-based guidelines for the laboratory diagnosis of GD have been published. The objectiveof the guidelines presented here is to provide evidence-based recommendations for the technical implementationand interpretation of biochemical and genetic testing for the diagnosis of GD to ensure a timely and accurate diag‑nosis for patients with GD worldwide. The guidelines have been developed by members of the Diagnostic Workinggroup of the International Working Group of Gaucher Disease (IWGGD), a non-proft network established to promoteclinical and basic research into GD for the ultimate purpose of improving the lives of patients with this disease. One ofthe goals of the IWGGD is to support equitable access to diagnosis of GD and to standardize procedures to ensure anaccurate diagnosis. Therefore, a guideline development group consisting of biochemists and geneticists working inthe feld of GD diagnosis was established and a list of topics to be discussed was selected. In these guidelines, twentyrecommendations are provided based on information gathered through a systematic review of the literature and twodiferent diagnostic algorithms are presented, considering the geographical diferences in the access to diagnosticservices. Besides, several gaps in the current diagnostic workfow were identifed and actions to fulfll them weretaken within the IWGGD. We believe that the implementation of recommendations provided in these guidelines willpromote an equitable, timely and accurate diagnosis for patients with GD worldwide.