Hurler syndrome is the most severe form of Mucolysaccharidosis Type I. All forms of MPS I are due to deficiency of the alpha-L-iduronase enzyme. Features are typical of most MPS disorders and include stunted growth, intellectual disability, loss of physical skills, cloudy cornea, joint stiffness, cardiac valvular problems, inguinal and umbilical hernias, distinct facial features, hepatosplenomegaly, upper respiratory tract infections, chronic ear infections leading to deafness, and spinal skeletal anomalies. Most patients do not survive up to 10-years of age and succumb to obstructive airway disease, respiratory infections, or cardiac complications.
Patients with MPS I are deficient in activity of the alpha-L-iduronidase enzyme. This enzyme plays a vital role in the metabolism of mucoplysaccharides by hydrolyzing unsulfated alpha-L-idurosidic linkages in dermatan sulfate. When mutations in the IDUA gene cause defects in the functioning of this enzyme, the glycosaminoglycans (mucopolysaccharides) are unable to be broken down properly, resulting in an accumulation of heparin sulfate and dermatan sulfate within the body tissues.
