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 degeneration, 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). Bone marrow transplantation may slow the progression of Hurler syndrome, but it is too early to know if it will be an effective treatment. Attempts at enzyme replacement therapy have not been successful to date. Hurler syndrome is also known as mucopolysaccharidosis I.

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the prototype of the mucopolysaccharidoses, and the gravest of the three allelic disorders of mucopolysaccharidosis I. It is caused by deficiency of L-iduronidase, and onset is after the first year with progressive physical and mental deterioration; there is corneal clouding, with death usually by age 10 caused by respiratory infection and heart failure. Further symptoms include gargoyle-like facies with hypertelorism, depressed nasal bridge, large tongue, and widely spaced teeth; dwarfism; severe somatic and skeletal changes, including short neck and trunk, scaphocephaly, and kyphosis with gibbus; short broad hands with short fingers; progressive opacities of the cornea; deafness; cardiovascular defects; hepatosplenomegaly; and joint contractures. Called also mucopolysaccharidosis IH.

Hurler syndrome. Child showing typical coarsening of facial features including prominent forehead, flattened nasal bridge, short broad nose, and widening of the lips.