Hurler syndrome

Hurler syndrome: An inherited error of metabolism in which there is deficiency of the enzyme alpha-L-iduronidase which normally breaks down molecules called mucopolysaccharides. Without the activity of this enzyme, there is an abnormal accumulation of mucopolysaccharides in the tissues of the body.

There are 2 clinical subtypes of disease due to deficiency of alpha-L-iduronidase: Hurler syndrome and Scheie syndrome. Hurler syndrome patients have progressive mental retardation, gross facial features, enlarged and deformed skull, small stature, corneal opacities, hepatosplenomegaly (enlargement of the liver and spleen), valvular heart defects, thick skin, joint contractures, and hernias.

Scheie syndrome patients have stiff joints, clouding of the cornea, aortic regurgitation (reflux through the aortic valve in the heart), and survival to a late age with little if any impairment of intellect.

There is a disease of intermediate severity due to the presence of one Hurler mutation and one Scheie mutation. The disease is termed Hurler-Scheie syndrome.

Hurler syndrome and Scheie syndrome are inherited in an autosomal recessive manner. The gene encoding alpha-L-iduronidase is on chromosome 4 (in band 4p16.3).

The first successful bone marrow transplant for Hurler syndrome was done in 1981. The procedure requires total-body radiation before the transplant. It is an effective treatment for the physical aspects of Hurler syndrome, except for the bone and eye disease. More recently, umbilical cord blood has been used for transplants in Hurler syndrome. Umbilical cord blood from unrelated donors provides stem cells for transplantation. This does not require total-body irradiation, and appears as effective as bone marrow transplantation. Enzyme replacement can also be done using recombinant alpha-L-iduronidase.

There is a choice of three treatments for Hurler syndrome -- bone marrow transplant, cord blood transplant, and enzyme replacement using recombinant alpha-L-iduronidase. The choice depends on the severity of Hurler syndrome, the clinical features of the case, and the age of the child.

The syndrome is named for the German pediatrician Gertrud Hurler who first described the disease in 1919. It is also known as mucopolysaccharidosis type I or MPS type I.