Deficient activity of the enzymes leads to abnormal cellular function as the partially degraded GAGs accumulate in the cells. As GAGs accumulate in cells of the connective tissue, the gradual appearance of the clinical features unfolds. As a result of the deficiency, an increase in the urinary excretion of DS and HS occurs in type I-H patients. A progressive physical and mental deterioration occurs after the onset of Hurler symptoms, usually around age 1 year. Maximum functional development of the child usually is reached when the child is aged 2-4 years.
Orthopedic complications are common, leading to pain and immobility.
Death usually occurs by age 14 years and usually is due to obstructed airway diseases, cardiac complication, or respiratory infections. No sex predilection exists. At birth, inguinal and umbilical hernias may be present. Physical and mental development delays appear about the time of the appearance of craniofacial abnormalities. I-H is the most clinically severe type of the MPSs.