This group of lysosomal deficiency diseases is probably the most common. MPS I is clinically heterogeneous encompassing three clinical entities: Hurler, Hurler-Scheie, and Scheie. In terms of clinical severity, Hurler is the most severe and Scheie is the mildest. Infants generally appear normal at birth and develop the typical coarse facial features in the first few months of life. Physical growth often stops at about 2 years of age. Skeletal changes of dysostosis multiplex are often seen and kyphoscoliosis is common as vertebrae become flattened. The head is large with frontal bossing and a depressed nasal bridge. Cranial sutures, especially the metopic and sagittal sutures, often close prematurely. The lips are prominent and an open mouth with an enlarged tongue is characteristic. The neck is often short. Odontoid hypoplasia increases the risk of vertebral subluxation and cord compression. Joints are often stiff and arthropathy eventually affects all joints. Claw deformities of the hands and carpal tunnel syndrome are common. Most patients are short in stature and barrel-chested.
Cardiac valves often are thickened and endocardial fibroelastosis is frequently seen. The coronary arteries are often narrowed. Respiratory obstructions are common and respiratory infections can be serious problems. Hearing loss is common.
Most patients reach a maximum functional age of 2 to 4 years and then regress. Language is limited. Untreated, many patients die before 10 years of age.
