Alpha-Iduronidase Enzyme Activity - Mucopolysaccharidosis Type I

Content Review: January 2022 Last Update: January 2022
Screening

Recommended initial test to screen for all mucopolysaccharidosis types, including MPS I

Diagnosis/Monitoring

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

Use to confirm a diagnosis of MPS I or to monitor glycosaminoglycan (GAG) levels in patients with confirmed MPS I

Use to confirm a diagnosis of MPS I or to monitor GAG levels in patients with confirmed MPS I

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

  • Attenuated MPS I: 1/500,000 
  • Severe MPS I: 1/100,000 

Genotype/Phenotype Correlation

MPS I Subtype Characteristics

Attenuated MPS I

Variants are often milder (eg, single base-pair substitutions)

  • Some residual enzyme function is retained

Severe MPS I

Associated with more severe, nonsense variants

  • Profound alpha-iduronidase deficiency

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

Additional Resources

  • 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.