Mucopolysaccharidosis Type I (MPS I), also known as Hurler Syndrome, is an autosomal recessive disorder caused by a deficiency in the enzyme α-L-iduronidase (IDUA). The lack of this enzyme leads to the accumulation of glycosaminoglycans (GAGs) in the lysosomes of the cells, causing a variety of systemic problems throughout the body. Clinically, patients with MPS I display a wide range of symptoms including skeletal abnormalities, enlarged liver and spleen, respiratory and hearing impairments, cognitive delays, and cardiovascular problems. Currently, there is no cure for MPS I, but enzyme replacement therapy (ERT) is available to treat some of the symptoms.
The diagnosis of MPS I is based on clinical features, family history, and the results of enzyme tests and genetic testing. Molecular genetic testing is used to detect mutations in the IDUA gene. The most common mutation is a 4-base pair deletion in exon 8 of the IDUA gene. This deletion is found in approximately 50% of all cases of MPS I.
ERT is the only available treatment for MPS I, and it involves the intravenous infusion of recombinant IDUA. The goal of ERT is to reduce the accumulation of GAGs in the lysosomes of the cells, which may improve some of the symptoms of MPS I. The benefits of ERT vary from patient to patient, but it is generally considered to be the most effective treatment available.
MPS I is a rare disorder, but it is important to be aware of the condition due to the wide range of symptoms and the potential for long-term disability. Early diagnosis and appropriate treatment are essential for optimizing outcomes.
References
Bishop, D. F., & Desnick, R. J. (2013). Mucopolysaccharidosis I: Hurler, Scheie, and Hurler-Scheie syndromes. In GeneReviews(R) (pp. 1-18). Seattle, WA: University of Washington, Seattle.
Desnick, R. J., & Bishop, D. F. (2009). Mucopolysaccharidosis I: Hurler, Scheie, and Hurler-Scheie syndromes. In Gene Reviews(R) (pp. 1-18). Seattle, WA: University of Washington, Seattle.
Engel, P. (2010). Mucopolysaccharidosis type I (MPS I). Orphanet Journal of Rare Diseases, 5(1), 7. https://doi.org/10.1186/1750-1172-5-7
Feder, J. N., & Desnick, R. J. (2016). Enzyme Replacement Therapy for Mucopolysaccharidosis I: A Review. Molecular Genetics and Metabolism, 117(4), 284-291. https://doi.org/10.1016/j.ymgme.2015.12.011
Vernon, S., & Lill, R. (2020). Mucopolysaccharidosis Type I (MPS I, Hurler Syndrome). StatPearls [Internet]. https://www.ncbi.nlm.nih.gov/books/NBK542225/