These syndromes are part of the family of disorders known as mucopolysaccharidoses, so-called because mucopolysaccharides, composed of long chains of sugar molecules, accumulate in cells throughout the body as the result of gene mutations causing enzyme deficiencies. This group was originally separated into Hurler syndrome named after Gertoud Hurler, a German pediatrician, and Scheie syndrome named after the American ophthalmologist Harold Glendon Scheie. Today we understand that mutations in a single gene are responsible for at least three clinically distinct disorders.
At least three forms of Hurler-Scheie syndrome with similar features have been proposed. These are: Hurler syndrome, Hurler-Scheie syndrome, and Scheie syndrome in decreasing order of clinical severity. Clouding of the cornea (windshield of the eye) is seen in all cases, with onset in early childhood and progressing to cause severe interference of vision. The light sensing tissue (retina) of the eye is also impacted and suffers functional damage. Some young children have glaucoma as well. The optic nerve may be swollen early and later becomes pale and has reduced function.
Most infants appear normal at birth but in a few months undergo physical changes such as coarsening of facial features and head enlargement that suggest the diagnosis. Physical growth ceases at about 3 years of age and most patients are therefore short in stature. The neck appears short. Vertebrae become flattened and abnormal curvature of the spine is common. The hands develop a claw-like configuration and joints are stiff. Carpal tunnel syndrome is common. The lips are large and an open mouth with an enlarged tongue is typical. Heart valves are involved and often do not operate properly. Breathing restrictions often lead to repeated infections of the respiratory tract. The liver and spleen are often enlarged.
Developmental delays are universal with most individuals reaching a functional age of 2 to 4 years before regressing. Untreated, many patients die before the age of 10 years. Hearing loss is common and language is usually limited.
These conditions are the result of a gene mutation which causes dysfunction in an enzyme important to the breakdown of long chain sugar molecules known as mucopolysaccharides. As a result, these accumulate in cells causing them to malfunction. The disease requires the presence of two mutations of the same gene and follows an autosomal recessive pattern of inheritance. Each parent who carries a single mutation is clinically normal but when both male and female contribute the same mutation to their child, disease results. The risk to subsequent children is 25% for each one.
The diagnosis is likely made by a pediatrician, often with the collaboration of a neurologist, ophthalmologist, and orthopedist. Growth delay, neurological regression, cloudy corneas, and skeletal deformities in combination suggest the diagnosis. Enlargement of the spleen and liver helps to confirm it.
These conditions have a poor prognosis. While starting out life apparently normal, neurological disease in the form of developmental delays are soon evident. Deformities in the face, hands, and trunk and slowing physical growth also become visible.
While no cure is available, promising therapies are on the horizon. Bone marrow transplantation and enzyme replacement therapies (Aldurazyme® ), if administered early, can improve walking and breathing and may slow progression of the neurological deterioration. Gene therapy may eventually become available.