Various guidelines for Gaucher disease have been developed, each stating that a diagnosis is based on the measurement of glucocerebrosidase enzyme activity in leukocytes or skin fibroblasts; enzymatic activity can also be measured using a screening assay in dried blood spots.1-8 A genetic analysis can identify the mutations or alterations in the GBA1 gene.1-5,7,9 The most frequent GBA1 mutations are N370S (c.1226A>G; p.Asp409Ser) and L444P (c.1448T>C; p.Leu483Pro). The N370S (c.1226A>G; p.Asp409Ser) mutation is associated with Gaucher disease Type 1 and the L444P (c.1448T>C; p.Leu483Pro) mutation with Gaucher disease Type 3.10,11 There may be overlap in glucocerebrosidase enzyme activity between heterozygote carriers of GBA1 gene mutations and healthy unaffected individuals without Gaucher disease. Therefore, genetic analysis studies are useful, especially in cases where measurement of glucocerebrosidase activity is inconclusive.12 Genetic analysis can also highlight the disease phenotype and risk for the neuronopathic forms of the disease (Types 2 and 3), as patients homozygous for the L444P (c.1448T>C; p.Leu483Pro) mutation have a higher risk for neurological impairment.13

Since Gaucher disease Type 1 has a higher birth incidence in the Ashkenazi Jewish population,14,15 carrier testing and prenatal screening can be offered to couples of Ashkenazi Jewish ethnicity, generally in a primary care obstetrical setting, to determine the risk for having children affected with Gaucher disease.16 Carrier couples are offered genetic consultations to discuss their reproductive options, where prenatal diagnosis is explained.17

Although the ‘gold standard’ for Gaucher disease diagnosis is the measurement of glucocerebrosidase enzyme activity,12,18 plasma levels of glucosylsphingosine (lyso-Gb1), chitotriosidase and CC chemokine ligand 18 (CCL18) have been shown to be elevated in patients with Gaucher disease, highlighting their use as disease biomarkers.19-26 In one study, levels of glucosylsphingosine (lyso-Gb1) in dried blood spots have also been used to identify patients with Gaucher disease. Patients with the neuronopathic form of the disease (Types 2 or 3) exhibited significantly higher levels of glucosylsphingosine (lyso-Gb1) than patients with non-neuronopathic Gaucher disease Type 1. This finding suggests that, in addition to being a biomarker of Gaucher disease, glucosylsphingosine (lyso-Gb1) may be useful for prenatal diagnosis and in screening programmes using dried blood spots.27

The availability of tests for Gaucher disease varies worldwide; more information is provided on the Genetic Testing Registry (

To aid clinicians in reaching a diagnosis of Gaucher disease, diagnostic algorithms have been published, and validated disease severity indexes are available to aid symptom monitoring.28-32 Following a diagnosis of Gaucher disease, subsequent evaluations may also include5:

  • Clinical and laboratory tests (blood count, clinical chemistry including transaminases, renal function and blood gas analysis)
  • Diagnostic imaging to determine liver and spleen sizes, and of skeletal pathology depending on symptoms.
  • Additional clinical and neurological examinations including neuro-ophthalmological testing, electroencephalogram (EEG; if necessary), brainstem auditory evoked potentials (AEP), magnetic resonance imaging (MRI) and cognitive performance tests.
  • Additional neurological examinations including eye movement tests to check for oculomotor apraxia, MRI, EEG, AEP, neuropsychological tests and cognitive performance tests.

C-ANPROM/INT//7567; Date of preparation: September 2020