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In Vitro Enzyme Measurement to Test Pharmacological Chaperone Responsiveness in Fabry and Pompe Disease
Published on: December 20, 2017
Diagnosing lysosomal storage disorders: Fabry disease.
Olaf A Bodamer1, Britt Johnson, Angela Dajnoki
1Division of Clinical and Translational Genetics, Dr. John T. MacDonald Foundation, Department of Human Genetics, University of Miami Miller School of Medicine, Miami, FL, USA.
Current Protocols in Human Genetics
|April 19, 2013
Summary
Fabry disease (FD) diagnosis is simplified for males using alpha galactosidase A (GLA) enzyme analysis in dried blood spots. This study details a tandem mass spectrometry method for accurate GLA activity measurement in DBS.
Area of Science:
- Biochemistry
- Genetics
- Lysosomal Storage Disorders
Background:
- Fabry disease (FD) is an X-linked lysosomal storage disorder caused by alpha galactosidase A (GLA) deficiency.
- Intralysosomal accumulation of glycosphingolipids leads to multi-organ damage in affected males and females.
- Current FD diagnosis relies on GLA analysis in leukocytes or dried blood spots (DBS) for males, but GLA activity can be normal in females.
Purpose of the Study:
- To provide a detailed analytical protocol for measuring GLA activity in DBS using tandem mass spectrometry.
- To facilitate high-throughput screening and diagnosis of Fabry disease, particularly in at-risk populations and newborns.
Main Methods:
- Enzyme analysis of alpha galactosidase A (GLA) activity in dried blood spots (DBS).
- Utilizing tandem mass spectrometry for precise and high-throughput measurement.
- Detailed analytical protocol development for GLA activity quantification.
Main Results:
- Tandem mass spectrometry offers a simplified and efficient diagnostic approach for FD males using DBS.
- The developed protocol enables accurate measurement of GLA enzyme activity.
- This method aids in high-throughput screening of newborns and at-risk populations.
Conclusions:
- Tandem mass spectrometry analysis of GLA activity in DBS is a valuable tool for diagnosing Fabry disease in males.
- The detailed protocol facilitates standardized and efficient diagnostic testing.
- Further application of this method can improve early detection and management of Fabry disease.
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