Mucopolysaccharidosis Type I (IDUA)
Mucopolysaccharidosis type I, also known as Hurler syndrome, is a pan-ethnic, autosomal recessive disease caused by pathogenic variants in the gene IDUA. This gene encodes the enzyme alpha-L-iduronidase, which breaks down specific molecules in cell lysosomes. When this enzyme does not function properly, excess molecules are retained in the lysosomes of various cells in the body. This storage disorder results in progressive symptoms including coarsening of the facial features, skeletal dysplasia, excess organ size, intellectual disability, vision impairment and hearing loss. Growth is stunted and death occurs due to failure of the heart and lungs, usually by the age of 10 years. Some patients have a milder disease course, which may be called Hurler-Scheie or Scheie syndrome. In this form, the disease is course is variable; some patients may die of complications in young adulthood, whereas others may life a natural lifespan with no major intellectual disability. Skeletal abnormalities and cardiac disease are usually the most severe symptoms in this form of the disease. The milder form of the disease occurs when at least one variant results in some residual enzyme activity, but not all pathogenic variants will allow for the prediction of disease severity.
For information about carrier frequency and residual risk, please see the residual risk table.