High-risk screening for Gaucher disease in patients with neurological symptoms

J Hum Genet. 2018 Jun;63(6):717-721. doi: 10.1038/s10038-018-0438-7. Epub 2018 Mar 30.

Abstract

Gaucher disease (GD) is an autosomal recessive lysosomal storage disorder caused by the deficiency of glucocerebrosidase enzyme activity. Clinical phenotypes of GD are categorized into three groups: (i) non-neuronopathic GD (type 1), (ii) acute neuronopathic GD (type 2) and (iii) subacute neuronopathic GD (type 3). The high-risk screening of neuronopathic GD has been performed using an enzymatic assay on the dried blood spot (DBS) samples. We enrolled a total of 102 individuals (47 females, 55 males; 0-57 years old; median age 10.5 years) with various neurological symptoms. We detected two patients with very low enzyme activity and they were diagnosed with the disease by using glucocerebrosidase gene analysis. Patient 1 was found to be compound heterozygous for the p.R159W/p.R170C locus and patient 2 was found to harbor two mutations at the IVS7+1G>T (c.999+1G>T) and p.L483P sites. This simple screening protocol using DBS samples is useful for early diagnosis of GD in high-risk and underdiagnosed patients suffering from various neurological symptoms.

Publication types

  • Case Reports

MeSH terms

  • Adolescent
  • Adult
  • Child
  • Child, Preschool
  • Early Diagnosis
  • Female
  • Gaucher Disease / blood
  • Gaucher Disease / diagnosis*
  • Gaucher Disease / genetics
  • Gaucher Disease / physiopathology
  • Genetic Predisposition to Disease
  • Genetic Testing / methods*
  • Glucosylceramidase / blood
  • Glucosylceramidase / genetics*
  • Glucosylceramidase / metabolism
  • Heterozygote
  • Humans
  • Infant
  • Infant, Newborn
  • Male
  • Middle Aged
  • Mutation
  • Phenotype
  • Young Adult

Substances

  • Glucosylceramidase