Contributor: Gordon K. Klintworth
Mucopolysaccharidosis type I-H (Hurler syndrome, OMIM #60714) is one type of mucopolysaccharidosis. This syndrome is an autosomal recessive disease caused by a mutation in the IDUA gene which encodes for α-L-iduronidase. A deficiency of this enzyme caused by mutations in the same gene also cause mucopolysaccharidosis type I-S and mucopolysaccharidosis type I-H/S. These three disorders vary in severity with mucopolysaccharidosis type I-H being the most serious, and mucopolysaccharidosis type I-S the least severe. A separate genetic mutation seems to be responsible for these two disorders as only one clinical phenotype develops in affected families. A pigmentary retinopathy and optic atrophy are common; rarely, papilledema follows increased intracranial pressure.The ocular manifestations of mucopolysaccharidosis type I-S include corneal clouding, a pigmentary retinopathy, bilateral narrow or closed angle glaucoma, and chronic papilledema with optic atrophy. By light microscopy the keratocytes as well as the basal epithelial cells in the cornea are vacuolated and stain with reagents that demonstrate glycosaminoglyycans. In some cases of mucopolysaccharidosis type I-S Bowman layer has been markedly attenuated, but this has not been an invariable finding. These conditions vary in severity with mucopolysaccharidosis type I -H being the most serious, and mucopolysaccharidosis type I -S the least severe. A separate genetic mutation seems to be responsible for these two disorders as only one clinical phenotype develops in affected families.Striking physical abnormalities characterize the phenotype of mucopolysaccharidosis type I-H. These include a grotesque facies with a prominent brow, an oversized tongue, a large saddle-shaped nose with broad nostrils, and a short neck associated with dwarfism, limitations in the mobility of joints, a protuberant abdomen with hepatomegaly, splenomegaly, umbilical and/or inguinal hernias, cardiac abnormalities, deafness and mental retardation. Skeletal abnormalities of the vertebrae are accompanied by a large shallow sella turcica, and broad stubby fingers due to hyperplastic terminal pharyngeal bones.

Infants with mucopolysaccharidosis type I-H may appear normal at birth, but have inguinal or umbilical hernias. Corneal clouding and the other characteristic physical findings of mucopolysaccharidosis type I-H are seldom recognized until 6 to 24 months after birth. Yet an abnormal accumulation of GAGs within the tissue has been confirmed in fetuses with mucopolysaccharidosis type I-H aborted at 20 weeks gestation. Excessive dermatan sulfate and heparan sulfate are excreted in the urine and, interestingly, the disease affects cartilage, bone and the cornea, tissues not normally containing these GAGs. In mucopolysaccharidosis type I-H, death usually ensues before the reproductive age is reached.

Patients with mucopolysaccharidosis type I-S manifest deformities of the hands and feet, coarse facies, and hirsutism. Intellect is not impaired and some affected individuals have been of more than normal intelligence. Their life span is normal, but most patients with this condition have aortic regurgitation due to aortic valve disease. The frequent deformities of the hand result from compression of the median nerve as it passes through the wrist (carpal tunnel syndrome). Yet, despite the clinical differences between mucopolysaccharidosis type I-H and mucopolysaccharidosis type I-S, these conditions resemble each other biochemically. The ocular manifestations of mucopolysaccharidosis type I-S include corneal clouding, a pigmentary retinopathy, bilateral narrow or closed angle glaucoma, and chronic papilledema with optic atrophy. By light microscopy the keratocytes as well as the basal epithelial cells in the cornea are vacuolated and stain with reagents that demonstrate glycosaminoglyycans. In some cases of mucopolysaccharidosis type I-S Bowman layer has been markedly attenuated, but this has not been an invariable finding.
Histologically, the lesions in mucopolysaccharidosis type I-S are indistinguishable from those in mucopolysaccharidosis type I-H. Multiple single membrane-delimited vacuoles containing fibrillogranular material appear in fibroblasts and the epithelium of the conjunctiva in mucopolysaccharidosis type I-S.

 
A diffuse cloudy luster occurs, particularly in the central cornea in mucopolysaccharidosis type I-H. This opacification reflects an abnormal accumulation of glycosaminoglycans in the cornea demonstrable with histochemical methods. By light microscopy the epithelium, fibroblasts (keratocytes)(especially beneath the epithelium) and endothelium of the cornea contain stored material. When examined by TEM the affected corneal cells contain fibrillogranular or amorphous material and occasional myelin figures, within numerous small, round or oval membrane-bound vacuoles. Long-spacing collagen is sometimes evident in the stroma. The lesions in canine mucopolysaccharidosis type I are virtually identical to those in humans, but in contrast to humans with mucopolysaccharidosis type I-H the corneal epithelium of affected dogs has been unremarkable. Corneal clouding has cleared in humans and dogs with mucopolysaccharidosis type I-H following bone marrow transplantation. A pigmentary retinopathy and optic atrophy are common; rarely, papilledema follows increased intracranial pressure.