Mucopolysaccharidoses

Mucopolysaccharides (MPS) or glycosaminoglycans (GAGs) consist of polysaccharide chains attached to a polypeptide core. Due to deficient activities of specific enzymes, MPSs accumulate in visceral organs and mesenchymal tissues and are excreted in urine. The mucopolysaccharides that are stored and excreted in urine are dermatan sulfate, heparan sulfate, and chon-droitin sulfate.

Mucopolysaccharidoses, common lysosomal diseases, affect chiefly infants and young children and are transmitted in an autosomal recessive fashion except for Hunter's disease, which has an X-linked recessive inheritance. Characteristic facial and skeletal abnormalities, cardiomyopathy, hepatosplenomegaly, corneal opacity, hearing impairments, and mental retardation are prominent clinical features. Several types of MPSs are distinguished based on specific enzyme defects, stored products, and clinical expression.

Hurler's disease (MPS1) is the model of mucopolysaccharidoses. The disease is caused by a deficiency of the enzyme a-L-iduronidase, encoded by a gene located on chromosome. 4. The enzyme deficiency results in an accumulation of dermatan sulfate and heparan sulfate in affected organs, and their excretions in the urine. The physical appearance of the affected infant has been compared to that of a gargoyle: coarse facial feature, a large scaphocephalic head with frontal bossing, coarse hair, depressed nasal bridge, thick eyebrows, and a thick tongue protruding through an open mouth. Dwarfism is evident by 3 to 4 years of age (Fig. 9.8). Dorsolumbar kyphosis is present, and the hands and fingers are broad. Bony abnormalities and skeletal changes are referred to as dysostosis multiplex. Skull radiographs show enlargement of the sella. Mental retardation, corneal opacity, cardiomegaly, hepatosplenomegaly, and umbilical hernia

Coarse Facial Features

figure 9.8

Hurler's disease. A and B. Pictures of a mentally retarded girl show the characteristic facial and skeletal features of the disease at ages 9 and 13 years. At age 13, she died of pulmonary infection. Note the short stature, large head, coarse facial features, thick tongue, and short neck. C. Transverse section of the brain shows dilated ventricles, focal thickening of the leptomeninges, and dilated perivascular spaces. D. Neuronal storage of PAS-positive material is moderate (PAS stain). E. The dilated pericapil-lary spaces are filled with a fine mesenchymal network (HE).

figure 9.8

Hurler's disease. A and B. Pictures of a mentally retarded girl show the characteristic facial and skeletal features of the disease at ages 9 and 13 years. At age 13, she died of pulmonary infection. Note the short stature, large head, coarse facial features, thick tongue, and short neck. C. Transverse section of the brain shows dilated ventricles, focal thickening of the leptomeninges, and dilated perivascular spaces. D. Neuronal storage of PAS-positive material is moderate (PAS stain). E. The dilated pericapil-lary spaces are filled with a fine mesenchymal network (HE).

are commonly present. Recurrent infections, spinal cord compression, and peripheral nerve entrapment are frequent complications.

Grossly, the brain is large and shows leptomeninges thickened from deposits of mucopolysaccharides in vascular endothelium and fibrous tissue. The ventricles are enlarged due to communicating obstructive hydroceph-alus. The histology is characterized by the neuronal storage of a mixture of gangliosides that stain positively for lipids and carbohydrates. Dilated perivascular spaces are filled with foamy macrophages (see Fig. 9.8).

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