The diagnosis and management of Gaucher disease in pediatric patients: Where do we go from here?

Gaucher disease (GD) is an autosomal recessive inherited lysosomal storage disease that often presents in early childhood and is associated with damage to multiple organ systems. Many challenges associated with GD diagnosis and management arise from the considerable heterogeneity of disease presentations and natural history. Phenotypic classification has traditionally been based on the absence (in type 1 GD) or presence (in types 2 and 3 GD) of neurological involvement of varying severity. However, patient management and prediction of prognosis may be best served by a dynamic, evolving definition of individual phenotype rather than by a rigid system of classification. Patients may experience considerable delays in diagnosis, which can potentially be reduced by effective screening programs; however, program implementation can involve ethical and practical challenges. Variation in the clinical course of GD and an uncertain prognosis also complicate decisions concerning treatment initiation, with differing stakeholder perspectives around efficacy and acceptable cost/benefit ratio. We review the challenges faced by physicians in the diagnosis and management of GD in pediatric patients. We also consider future directions and goals, including acceleration of accurate diagnosis, improvements in the understanding of disease heterogeneity (natural history, response to treatment, and prognosis), the need for new treatments to address unmet needs for all forms of GD, and refinement of the tools for monitoring disease progression and treatment efficacy, such as specific biomarkers.

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Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.

Déclaration de conflit d'intérêts

Declaration of Competing Interest NJW has consulted for Pfizer, Sanofi Genzyme and Takeda, has participated in speaking engagements for Sanofi Genzyme, and is a member of the data safety monitoring board for AVROBIO. OG-A has served on advisory boards and received consulting fees from 4DMT, Amicus Therapeutic, Sangamo Therapeutics, Sanofi Genzyme and Takeda, has research contracts with 4DMT, Amicus Therapeutics, AVROBIO, Freeline Therapeutics, Genentech, Protalix BioTherapeutics, Sangamo Therapeutics, Sanofi Genzyme and Takeda, and has participated in a speaker bureau for Sanofi Genzyme and Takeda. PSK has received research/grant support from Pfizer, Sanofi Genzyme and Takeda, has received consulting fees and honoraria from Sanofi Genzyme and Takeda, and is a member of the Gaucher Disease Registry Advisory Board for Sanofi Genzyme and the Advisory Board for Takeda. NL has participated in advisory boards and clinical trials for Amicus Therapeutics, Pfizer, Protalix BioTherapeutics, Sanofi Genzyme and Shire (a Takeda company). TAB is a member of the American Gaucher Disease Registry Board. He has participated in advisory board meetings for and received research funding, travel reimbursement, and honoraria for speaking from Sanofi Genzyme and Takeda. JAB receives research support from AVROBIO, BioMarin Pharmaceutical, Idorsia Pharmaceuticals, Pfizer, Protalix BioTherapeutics, Sangamo Therapeutics, Sanofi Genzyme and Takeda and has served on advisory boards for Sanofi Genzyme and Takeda. PG has participated in advisory boards and clinical trials for BioMarin Pharmaceutical, Pfizer, Sanofi Genzyme and Shire (a Takeda company) and is on the speaker bureau for Sanofi Genzyme. NH has nothing to disclose. HP has participated in advisory boards and/or speaking engagements and/or clinical trials for Alexion Pharmaceuticals, Amicus Therapeutics, AVROBIO, Sanofi Genzyme and Takeda. CP has consulted for Takeda and has participated in a speaker bureau for Sanofi Genzyme. DV has nothing to disclose. RRP is a full-time employee of Takeda and a stockholder of Takeda Pharmaceuticals Company Limited. EW is a full-time employee of Takeda and a stockholder of Takeda Pharmaceuticals Company Limited. CF has served as an advisor or consultant for Horizon Therapeutics, Orphan Technologies, Recordati, Sanofi Genzyme, Shire (a Takeda company) and Swedish Orphan Biovitrum. He has received grants for clinical research from Homology Medicines, Orphan Technologies, Passage Bio, REGENXBIO, Sanofi Genzyme, Takeda and Vtesse.