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- Glucosylsphingosine (lyso-Gb1) plays a central role in the diagnosis and proper assessment of disease severity in Gaucher patients
Glucosylsphingosine (lyso-Gb1) plays a central role in the diagnosis and proper assessment of disease severity in Gaucher patients
Gaucher disease (GD) is an autosomal recessive, rare genetic disorder characterized by the deposition of glucocerebroside in cells of the macrophagemonocyte system.
Materials and methods:
We have developed and systematically validated a high-throughput workflow for the simple testing of GD patients: beta-glucocerebrosidase enzymatic activity, glycosylsphingosine (lyso-Gb1) quantification in DBS followed by GBA gene sequencing from the sample blood sample. We report data from over 940 Gaucher individuals. Determination of lyso-Gb1 using LC/MRM-MS was investigated in three GBA cohorts comprising of: (A) 247 homozygotes GBA cases; (B) 308 compound heterozygotes GBA patients and (C) 305 Gaucher carriers. Lyso-Gb1 has a sensitivity and specificity of 100% for the primary diagnosis of GD. The clinical severity of the mutations and their location could be correlated with the lyso-Gb1 in the homozygous cases, e.g. c.1295G>T is correlated with mild lyso-Gb1 values while c.1060G>A and c.518C>A with extremely high lyso-Gb1 values ( > 600 ng/mL). The most common GBA mutations arec.1226A>G (34 %) and c.1448T>C (25.5 %). c.1448T>C is a severe mutation correlating to a massive increase of lyso-Gb1 up to 2,850 ng/mL. Lyso-Gb1 for c.1226A>G can vary from very mild to moderate.
Lyso-Gb1 concentrations in blood can be used for the easy, early and highly specific diagnosis of GD patients.
These findings were presented at the 13th International Congress Inborn Errors of Metabolism (ICIEM 2017).