Electrophoresis/Spectrophotometry
Recommended initial test to screen for all mucopolysaccharidosis types, including MPS I
Diagnosis/Monitoring
Quantitative Fluorometry
Recommended test to exclude MPS I following an abnormal screen or to confirm MPS I in patients with a consistent clinical phenotype and/or a positive family history
Liquid Chromatography-Tandem Mass Spectrometry
Use to confirm a diagnosis of MPS I or to monitor glycosaminoglycan (GAG) levels in patients with confirmed MPS I
Liquid Chromatography-Tandem Mass Spectrometry
Use to confirm a diagnosis of MPS I or to monitor GAG levels in patients with confirmed MPS I
Spectrophotometry
Use to monitor GAG levels in patients with confirmed MPS I
Disease Overview
Mucopolysaccharidosis type I (MPS I) is a progressive disorder that ranges in severity and can affect numerous systems throughout the body. Subtypes include attenuated MPS I (previously known as Hurler-Scheie and Scheie syndromes) and severe MPS I (formerly Hurler syndrome). Symptoms vary widely but can include cardiomyopathy, “coarse” facial features (eg, thickening of the earlobes, lips, outside of nostrils, and tongue), intellectual disability, organomegaly, and progressive skeletal dysplasia.
Genetics
Gene
IDUA
Inheritance
Autosomal recessive
Incidence
MPS I: ~1/70,000
Genotype/Phenotype Correlation
MPS I Subtype | Characteristics |
---|---|
Attenuated MPS I |
Variants are often milder (eg, single base-pair substitutions)
|
Severe MPS I |
Associated with more severe, nonsense variants
|
Test Interpretation
Results
An extremely low or undetectable level of alpha-iduronidase enzyme activity in leukocytes is consistent with MPS I.
Limitations
Testing for alpha-iduronidase enzyme activity:
- Cannot differentiate between attenuated MPS I (ie, Hurler-Scheie and Scheie syndromes) and severe MPS I (Hurler syndrome)
- Categorization depends on clinical and/or molecular genetic findings
- Cannot predict carrier status for MPS I
- Does not evaluate enzyme deficiencies in other MPS types
Additionally, pseudodeficiency has been demonstrated for this enzyme due to specific gene variants that affect the exogenous substrate but not endogenous substrates. Individuals with pseudodeficiency are not affected with MPS I.
References
-
GeneReviews - Mucopolysaccharidosis type I
Clarke LA. Mucopolysaccharidosis type I. In: Adam MP, Ardinger HH, Pagon RA, et al., eds. GeneReviews, University of Washington, Seattle; 1993-2022. [Last update: Feb 2021; Accessed: Jan 2022]
24675674
Beck M, Arn P, Giugliani R, et al. The natural history of MPS I: global perspectives from the MPS I Registry. Genet Med. 2014;16(10):759-765.
18201392
Clarke LA. The mucopolysaccharidoses: a success of molecular medicine. Expert Rev Mol Med. 2008;10:e1.
Lysosomal disorders. In Pediatric Endocrinology
Enns GM, Steiner RD, et al. Lysosomal disorders. In: Sarafoglou K, Hoffman GF, Roth KS, eds. Pediatric Endocrinology and Inborn Errors of Metabolism. McGraw-Hill Education/Medical; 2009:747-748.
22231271
Lawrence R, Brown JR, Al-Mafraji K, et al. Disease-specific non-reducing end carbohydrate biomarkers for mucopolysaccharidoses. Nat Chem Biol. 2012;8(2):197-204.
NORD - Mucopolysaccharidosis type I
National Organization for Rare Disorders (NORD). Mucopolysaccharidosis type I. [Published: 2019; Accessed: Jan 2022]
Screening