Abstract
Lysosomal Storage Diseases (LSD) are a group of genetic disorders where lysosomes cannot break down and eliminate large molecules from cells. There are nearly 50 diseases in this group, and many of them have symptoms similar to other common diseases, leading to misdiagnosis or delayed diagnosis for many patients. Complications often render patients disabled or lead to premature death. However, some diseases are treatable or can be cured if diagnosed early. Diagnosis based solely on genetic testing may encounter positions with variants of unknown significance (VUS), while enzyme activity tests may also yield false-positive results. Both tests cannot be used to monitor treatment outcomes. Therefore, this study aims todevelop biomarker quantitative analysis for two common treatable LSD, Gaucher disease (GD) and Pompe disease (PD), to provide patients in Thailand with more accurate and prompt diagnoses and to be used as a tool for monitoring treatment outcomes. Forty participants were included in the study: patients with GD (11), PD (4), carrier (6), and normal individuals (19). The study successfully developed assays for detecting glucosylsphingosine (Lyso-Gb1) from plasma and dried blood spots for GD and Glucose tetrasaccharide (Hex4) from urine for PD. The result revealed a significant elevation of Lyso-Gb1 in untreated GD patients (29.7 pmol/mL), approximately 100 times normal individuals (0.34 pmol/mL). Similarly, Hex4 levels were markedly higher, approximately 75 times, in untreated Pompe disease patients (44.7 µM) compared to healthy controls (0.59 µM). Moreover, treated patients exhibited decreased biomarker concentrations compared to untreated patients for both diseases. Notably, GD patients treated with hematopoietic stem cell transplantation showed lower Lyso-Gb1 concentrations than those treated with enzyme replacement therapy. Genetic analysis revealed a common mutation in the GBA gene among GD patients, with mutations detected in up to 86.4% of cases at position c.1448T>C (p.Leu483Pro). Genetic mutations were found in various positions within the GAA gene for PD. The study demonstrates the successful development of assays for detecting Lyso-Gb1 in GD and Hex4 in PD, serving as effective biological markers for diagnosis and treatment monitoring. The establishment of a testing facility for these biomarkers in Thailand addresses a critical gap in the availability of diagnostic resources and further research for LSD.
