250 cases of

Abstract

‘Type 2’ Gaucher disease, also referred to as ‘acute neuronopathic’ or ‘infantile’ Gaucher disease is an aggressive subtype of Gaucher disease, resulting from pathogenic variants in GBA1. The spectrum of phenotype ranges from hydropic perinatal presentations to an infantile disease characterised by rapid neurodegeneration. Increasingly, reports are offered of patients who survive into childhood, and it is unclear if these individuals represent a severe form of the type 3 (historically considered ‘juvenile’) disease or have modified outcomes resulting from contemporary medical interventions. Predicting outcome at point of diagnosis is increasingly important to families and clinicians, and while the impact of ‘severe’ or null alleles is appreciated, there remain significant uncertainties surrounding genotype-phenotype correlation. In an era of clinical trials and endeavors to find CNS modifying therapeutics, there is a need to be able to categorise and predict clinical outcomes more accurately. Here we report a case-series (n = 13) of internationally referred patients to a single centre, highlighting the spectrum of phenotype encompassed by the single nomenclature of ‘type 2 Gaucher’ disease. From this case-series we propose a new pragmatic, clinical classification system which could be applied to any infant at point of presentation. We subsequently applied this classification system to the historical literature and a further series of historical cases contributed by collaborators across the globe. We collated data from 250 cases, and demonstrate that it is feasible to apply this classification system and show that this has the potential to offer future genotype-phenotype correlation if expanded to a larger cohort.