Diagnosing neuronopathic Gaucher disease: New considerations and challenges in assigning Gaucher phenotypes

Mol Genet Metab. 2021 Feb;132(2):49-58. doi: 10.1016/j.ymgme.2021.01.002. Epub 2021 Jan 9.


Gaucher disease (GD), resulting from biallelic mutations in the gene GBA1, is a monogenic recessively inherited Mendelian disorder with a wide range of phenotypic presentations. The more severe forms of the disease, acute neuronopathic GD (GD2) and chronic neuronopathic GD (GD3), also have a continuum of disease severity with an overlap in manifestations and limited genotype-phenotype correlation. In very young patients, assigning a definitive diagnosis can sometimes be challenging. Several recent studies highlight specific features of neuronopathic GD that may provide diagnostic clues. Distinguishing between the different GD types has important therapeutic implications. Currently there are limited treatment options specifically for neuronopathic GD due to the difficulty in delivering therapies across the blood-brain barrier. In this work, we present both classic and newly appreciated aspects of the Gaucher phenotype that can aid in discriminating between acute and chronic neuronopathic GD, and highlight the continuing therapeutic challenges.

Keywords: GBA1; Gaucher disease; Glucocerebrosidase; Neuronopathic; Newborn screening; Next-generation sequencing.

Publication types

  • Research Support, N.I.H., Intramural
  • Review

MeSH terms

  • Blood-Brain Barrier / drug effects
  • Gaucher Disease / classification
  • Gaucher Disease / diagnosis*
  • Gaucher Disease / drug therapy
  • Gaucher Disease / genetics
  • Genetic Association Studies
  • Glucosylceramidase / genetics*
  • Humans
  • Phenotype
  • Severity of Illness Index


  • GBA protein, human
  • Glucosylceramidase