α-L-iduronidase (MPS I)
Related Gene(s): IDUA
Mucopolysaccharidosis type I (MPS I) is a progressive, multisystem condition that is divided into severe (formerly referred to as Hurler syndrome) and attenuated (formerly referred to as Hurler-Scheie syndrome and Scheie syndrome) types. The severe form occurs in approximately 1 in 100,000 newborns and the attenuated form occurs in approximately 1 in 500,000 newborns. The disorder in inherited in an autosomal recessive pattern and is caused by deficient activity of the lysosomal enzyme α-L-iduronidase.
α-L-iduronidase removes the non-reducing terminal α-L-iduronide residues during the lysosomal degradation of heparan sulfate and dermatan sulfate. Deficiency of α-L-iduronidase results in lysosomal storage of these glycosaminoglycans and a variable range of symptoms that affect many parts of the body. Symptoms of severe MPS I may include inguinal hernia, frequent upper respiratory infections before 1 year of age, coarse facies, progressive skeletal dysplasia, progressive and profound intellectual disability, and hearing loss. Death, usually caused by cardiorespiratory failure, typically occurs within the first ten years of life. Symptoms of attenuated MPS I are similar, though more variable and often include detectable learning disabilities.
The diagnosis of MPS I is established either by identification of two pathogenic variants in the IDUA gene through molecular analysis or detection of the severe deficiency of α-L-iduronidase activity. The pseudodeficiency alleles in the IDUA gene can result in reduced enzyme activity with the artificial or synthetic substrates in vitro. The α-L-Iduronidase activity is measured with a lysate from patient’s white blood cells (WBC) using a liquid chromatography and tandem mass spectrometry (LC-MS/MS) method. This enzyme analysis is not a reliable method for carrier determination. Carrier testing can be accomplished, however, through molecular analysis of the IDUA gene.
- Blood: 5-10 mL in ACD tube (yellow top) is preferred. Minimum of 3 mL is required. Sodium (or lithium) heparin tubes (green top) or EDTA tubes (lavender top) are also accepted
- 1-2 leukocyte pellets
- Ship whole blood at room temperature (sample must be received within 72 hours of collection)
- Ship leukocyte pellet(s) frozen on dry ice
- 7 days