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Diagnosing lysosomal storage disorders: mucopolysaccharidosis type I
Britt A Johnson1, Angela Dajnoki1, Olaf A Bodamer1
1Division of Clinical and Translational Genetics, Dr. John T. MacDonald Foundation, Department of Human Genetics, University of Miami Miller School of Medicine, Miami, Florida.
Current Protocols in Human Genetics
|January 21, 2015
Summary
Mucopolysaccharidosis type I (MPS I), a genetic disorder, is diagnosed by measuring alpha-L-iduronidase (IDUA) enzyme activity. Tandem mass spectrometry in dried blood spots offers a high-throughput method for early MPS I detection.
Area of Science:
- Biochemistry
- Genetics
- Metabolic Disorders
Background:
- Mucopolysaccharidosis type I (MPS I) is a lysosomal storage disorder caused by alpha-L-iduronidase (IDUA) deficiency.
- Accumulation of glycosaminoglycans leads to multisystemic symptoms, including skeletal deformities, intellectual disability, and organ enlargement.
Purpose of the Study:
- To provide a detailed analytical protocol for measuring IDUA enzyme activity in dried blood spots (DBS).
- To facilitate high-throughput screening for MPS I using tandem mass spectrometry.
Main Methods:
- Enzyme activity measurement of alpha-L-iduronidase (IDUA) in DBS.
- Utilizing tandem mass spectrometry for high-throughput analysis.
- Molecular confirmation of IDUA gene mutations for definitive diagnosis.
Main Results:
- Established a robust protocol for IDUA activity quantification in DBS.
- Demonstrated the utility of tandem mass spectrometry for efficient MPS I screening.
- Enabled early diagnosis in symptomatic individuals and newborns.
Conclusions:
- Tandem mass spectrometry provides an effective method for high-throughput IDUA enzyme analysis in DBS for MPS I screening.
- This protocol supports early detection and management of MPS I.
- Accurate enzyme activity measurement is crucial for diagnosing MPS I.
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