INTRODUCING
Fabry disease is a multisystemic disorder with a range of signs and symptoms, and should be considered in the differential diagnosis of many systemic diseases.
Why test for globotriaosylsphingosine (lyso-Gb3)?
In patients with Fabry disease, deficient activity of the lysosomal enzyme alpha-galactosidase A (α-Gal A) leads to an accumulation of the glycosphingolipids globotriaosylceramide (Gb3) and lyso-Gb3 within almost all cell types and various organs.1-3 Alterations in the enzyme activity of α-Gal A are a result of variants in the GLA gene.4Levels of lyso-Gb3 are markedly elevated in some patients with Fabry disease, highlighting its potential use as a diagnostic biomarker.4-6
What is the lyso-Gb3 assay?
Levels of lyso-Gb3 can be assessed in the plasma, urine or dried blood spots.7,8 Lyso-Gb3 is the deacylated form of Gb3.9 Evidence suggests that levels of lyso-Gb3 can be used for stratifying patients with either classical or late-onset Fabry disease, and as a marker of disease severity.10,11 In one study, the mean (standard deviation [SD]) plasma levels of lyso-Gb3 were elevated in patients with classical Fabry disease versus those with late-onset Fabry disease (38.7 [39.1] vs 0.8 [0.9] ng/mL; p<0.001).10 Furthermore, levels of lyso-Gb3 have been shown to correlate with the development of cerebrovascular white matter lesions in male patients and increased left ventricular mass in females, as well as decreased kidney function, renal replacement therapy, cardiomyopathy, and stroke and transient ischaemic attack.6,12 However, in female patients with late-onset Fabry disease, levels of lyso-Gb3 may overlap with levels in unaffected individuals without Fabry disease.11,13 Therefore, evaluation of lyso-Gb3 levels may be more useful in assessing disease severity in male patients with Fabry disease.12,14
How sensitive is the lyso-Gb3 assay in diagnosing Fabry disease?
The relative sensitivity of testing for plasma lyso-Gb3, α-Gal A enzyme activity in dried blood spots, and GLA gene sequencing for diagnosis of suspected Fabry disease in both males and females was assessed during a 2-year clinical diagnostics programme. The sensitivity of the assay for lyso-Gb3 for confirming a suspected diagnosis of Fabry disease was 98% in males and 97% in females. These results further suggest that plasma lyso-Gb3 is a sensitive assay for providing diagnostic information for Fabry disease. Testing for α-Gal A enzyme activity in males is considered the first step in the diagnostic work-up for Fabry disease, as the sensitivity of the enzyme assay for α-Gal A was 100% in males, but only 49% in females. Therefore, it is suggested that a diagnosis of Fabry disease in females can instead be more efficiently made using concurrent analysis of plasma lyso-Gb3 and GLA gene sequencing.15
C-ANPROM/INT/FAB/0016; Date of preparation: March 2021
Brochure
Due to the high prevalence of cardiac involvement in patients with Fabry disease, cardiologists are vital in the screening and diagnosis of the disease. Cardiologists are recommended to maintain an awareness of Fabry disease.
Brochure
Neurologists can aid an early diagnosis of Fabry disease and document neurological involvement associated with the disease.
DIFFERENTIAL DIAGNOSIS
How can alpha-galactosidase A (α-Gal A) enzyme activity be assessed in patients with Fabry disease?
In Fabry disease, deficient enzymatic activity of α-Gal A can be assessed using plasma, leukocytes, cultured fibroblasts or dried blood spots.
DIFFERENTIAL DIAGNOSIS
Why should patients with Fabry disease receive genetic testing?
Genetic testing is used to confirm a diagnosis of Fabry disease in female patients, and can be used to support a diagnosis in males.