DIAGNOSIS
MPS I diagnosis can be confirmed by demonstrating a low or absent alpha-L-iduronidase activity1,2
Urinary glycosaminoglycans (heparan sulfate and dermatan sulfate) measurement can provide helpful information and is often performed as an initial screening and a preliminary investigative test.
Other diagnostic tests may include:
Prenatal testing
MPS I can be diagnosed prenatally by measuring the enzyme activity in culture for amniocytes or in chorionic villi. It can also be diagnosed prenatally in leukocytes and plasma of fetal blood obtained by cordocentesis.3,4
Carrier testing
Carrier testing is indicated in family members if the pathogenic variants within the family are known. If not, the technologies available to assess gene pathogenic variants that underlie MPS I do not currently allow for routine carrier detection by molecular methods. The value of carrier testing to identify couples who may be at risk of having an affected child is also limited.4
Molecular genetic testing
Molecular genetic testing can detect disease-causing variants in the IDUA gene known to cause MPS I. Altered alleles need to be identified for the specific family before the molecular diagnosis can be undertaken for members at risk.4
DNA-based testing is the only definitive way to determine carrier status but will likely have limited value in individuals who are at low risk of being carriers.4
GAG = glycosaminoglycan; IDUA = α-L-iduronidase; MPS I = mucopolysaccharidosis type I.
References: 1. de Ru MH, Boelens JJ, Das AM, et al. Enzyme replacement therapy and/or hematopoietic stem cell transplantation at diagnosis in patients with mucopolysaccharidosis type I: results of a European consensus procedure. Orphanet J Rare Dis. 2011;6(55):1-9. 2. Wraith JE. The first 5 years of clinical experience with laronidase enzyme replacement therapy for mucopolysaccharidosis I. Expert Opin Pharmacother. 2005;6(3):489-506. 3. Hall CW, Liebaers I, Di Natale P, Neufeld EF. Enzymic diagnosis of the genetic mucopolysaccharide storage disorders. Methods Enzymol. 1978;50:439-456. 4. Neufeld EF, Muenzer J. The Mucopolysaccharidoses. In: Valle DL, Antonarakis S, Ballabio A, Beaudet AL, Mitchell GA. eds. The Online Metabolic and Molecular Bases of Inherited Disease. McGraw Hill; 2019. Accessed July 20, 2022. https://ommbid.mhmedical.com/content.aspx?bookid=2709&ectionid=225544161.