Mucopolysccharidoses are a group of rare, inherited lysosomal storage disorders caused by a deficiency of a lysosomal enzyme responsible for breaking down glycoaminoglycans or GAGs. The incidence of all MPSs disorders is approximately 1:50,000 to 1:25,000. The incidence of MPS I is approximately 1:100,000.
Each of the MPS disorders are listed below. The table outlines the associated genes and enzyme deficiencies in each of the MPS disorders.
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The GAGs that accumulate in each of the MPS disorders varies. The table below highlights which GAGs are elevated in each of the MPS disorders.
Adopted from Zschocke/Hoffmann, Vademecum Metabolicum – Manual of Metabolic Paediatrics; 2nd Edition
Mucopolysaccharidosis I (MPS I)
Mucopolysaccharidosis Type I (MPS I) is one of the seven mucopolysaccharidoses. It is an inherited, multisystem, progressive disorder caused by a deficiency of the lysosomal enzyme α-L-iduronidase, which is encoded by the IDUA gene. Pathogenic mutations to the IDUA gene lead to a defective enzyme with lesser than normal alpha-L-iduronidase activity. The decreased activity of this enzyme causes GAGs, particularly dermatan and heparan sulfate, to accumulate in the lysosome. Over time the build-up of dermatan and heparan sulfate leads to excess cellular storage and cellular dysfunction which ultimately leads to cell death and organ-specific clinical manifestations. The tissues and organs which are affected varies.
References: 1. Arn P, et al. J Pediatr. 2009; 154:859-64 e3. 2. Clarke LA. NCBI Bookshelf, a service of the National Library of Medicine, National Institutes of Health (NIH). Available at: https://www.ncbi.nlm.nih.gov/books/NBK1162/. Accessed July 20, 2018.
Systemic Effects of GAG Accumulation
The clinical severity of MPS I varies amongst patients and patients. MPS I patients are commonly categorized into one of three clinical groups depending upon their cognitive functioning. Patients with pronounced mental delays with loss of acquired skills are generally classified as Hurler or severe patients. Those with no to mild learning disabilities are commonly classified as Hurler-Scheie, and those with no cognitive impairments are classified as Scheie patients. Overall, all phenotypes across the MPS I spectrum are progressive and debilitating.
Multiple organ systems are affected in MPS I. The clinical presentation and organ involvement varies from patient to patient. Not all patients will experience the same symptoms. The figure below outlines some of the clinical presentations that can present in MPS I patients.
Muenzer J, et al. Pediatrics. 2009;123(1):19-29; Neufeld EF, Muenzer J. The mucopolysaccharidoses. In: Scriver CR, Beaudet AL, Sly WS, Valle D, eds. The Metabolic & Molecular Bases of Inherited Disease. New York, NY: McGraw-Hill; 2001:3421-3452; Vijay S, Wraith JE. Acta Paediatr. 2005;94(7):872-877; National MPS Society. A guide to understanding MPS I. http://mpssociety.org/wp-content/uploads/2011/07/booklet_MPS_I_v8.pdf. 2008.