Skip to Main Content

Chapter 39: Extracellular Matrix: Glycosaminoglycans and Proteoglycans

A male infant, delivered at 38 weeks' gestation, presents with severe bowing of long bones, blue sclera, and craniotabes at birth. Radiographs show severe generalized osteoporosis, a broad and crumpled long bones, beading ribs, and a poorly mineralized skull. Histologic examination of the long bones revealed the trabeculae of the calcified cartilage with an abnormally thin layer of osteoid, and the bony trabeculae are thin and basophilic. The symptoms observed in the infant are characteristic of which disease?

A. Ehlers-Danlos syndrome

B. Hunter syndrome

C. Hurler syndrome

D. Marfan syndrome

E. osteogenesis imperfecta

Answer E: Osteogenesis imperfecta consists of a group of at least 4 types (mild, extensive, severe, and variable). The disorder is characterized by brittle bones and abnormally thin sclerae, which appear blue owing to the lack of connective tissue. The symptoms arise due to defects in two α-collagen genes, the COL1A1 and COL1A2 genes. There have been over 100 mutations identified in these 2 genes. The mutations lead to decreased expression of collagen or abnormal pro1 proteins. The abnormal proteins associate with normal collagen subunits, which prevents the triple helical structure of normal collagen to form. The result is degradation of all the collagen proteins, both normal and abnormal.

A 30-month-old child presents with coarse facial features, corneal clouding, hepatosplenomegaly, and exhibiting disproportionate short-trunk dwarfism. Radiographic analysis indicates enlargement of the diaphyses of the long bones and irregular metaphyses, along with poorly developed epiphyseal centers. Other skeletal abnormalities typify the features comprising dysotosis multiplex. The child's physical stature and the analysis of bone development indicate the child is suffering from which of the following disorders?

A. Ehlers-Danlos syndrome

B. Hunter syndrome

C. Hurler syndrome

D. Marfan syndrome

E. osteogenesis imperfecta

Answer C: Although multiorgan involvement, liver and spleen enlargement, and skeletal abnormalities are common to all the mucopolysaccharidotic (MPS) diseases, each encompasses features that allow for specific diagnosis. Hurler syndrome is characterized by progressive multiorgan failure and premature death. Hallmark features include enlargement of the spleen and liver, severe skeletal deformity, and coarse facial features (which are associated with the constellation of defects referred to as dysotosis multiplex). The disease results from a defect in α-l-iduronidase activity, which leads to intracellular accumulations of heparan sulfates and dermatan sulfates. The accumulation of these GAGs (glycosaminoglycan) in Hurler syndrome patients severely affect development of the skeletal system leading, primarily, to defective long ...

Pop-up div Successfully Displayed

This div only appears when the trigger link is hovered over. Otherwise it is hidden from view.