keratan-sulfate and Syndrome

To describe the histopathology of the cornea in microphthalmia with linear streaks (MLS) syndrome.. Two patients with MLS syndrome underwent penetrating keratoplasty. This study describes the histopathology and investigates immunophenotype of the corneal extracellular matrix by using keratan sulfate and collagen type III antibodies.. Clinical examination revealed bilateral sclerocornea and characteristic skin changes. By light microscopy, central corneal stroma in both patients showed vascularization and irregular thick collagen lamellae typical of sclerocornea. In addition, corneal thinning, anterior synechiae, and the absence of the Descemet membrane were noted, which was suggestive of Peters anomaly. Diffuse and intense anti-keratan sulfate staining and minimal anti-collagen type III stromal staining were seen in both corneal buttons.. The cornea in MLS may clinically resemble sclerocornea. Histologic features resemble those previously described in sclerocornea and also seen in anterior segment dysgeneses. Keratan sulfate and collagen type III labeling suggests that the corneal extracellular matrix resembled cornea and not sclera.

Topics: Collagen Type III; Cornea; Corneal Opacity; Extracellular Matrix; Female; Fluorescent Antibody Technique, Indirect; Humans; Immunophenotyping; Infant; Keratan Sulfate; Keratoplasty, Penetrating; Male; Microphthalmos; Sclera; Skin Abnormalities; Syndrome

Lumican and fibromodulin regulate the assembly of collagens into higher order fibrils in connective tissues. Here, we show that mice deficient in both of these proteoglycans manifest several clinical features of Ehlers-Danlos syndrome. The Lum(-/-)Fmod(-/-) mice are smaller than their wild type littermates and display gait abnormality, joint laxity, and age-dependent osteoarthritis. Misaligned knee patella, severe knee dysmorphogenesis, and extreme tendon weakness are the likely causes for joint laxity in the double-nulls. Fibromodulin deficiency alone leads to significant reduction in tendon stiffness in the Lum(+/+)Fmod(-/-) mice, with further loss in stiffness in a Lum gene dose-dependent way. At the protein level, we show marked increase of lumican in Fmod(-/-) tendons, which may partially rescue the tendon phenotype in this genotype. These results establish fibromodulin as a key regulator and lumican as a modulator of tendon strength. A disproportionate increase in small diameter immature collagen fibrils and a lack of progression to mature, large diameter fibrils in the Fmod(-/-) background may constitute the underlying cause of tendon weakness and suggest that fibromodulin aids fibril maturation. This study demonstrates that the collagen fibril-modifying proteoglycans, lumican and fibromodulin, are candidate genes and key players in the pathogenesis of certain types of Ehlers-Danlos syndrome and other connective tissue disorders.

Topics: Animals; Base Sequence; Carrier Proteins; Chondroitin Sulfate Proteoglycans; DNA Primers; Extracellular Matrix Proteins; Fibromodulin; Joint Instability; Keratan Sulfate; Lumican; Mice; Mice, Inbred C57BL; Mice, Knockout; Microscopy, Electron; Proteoglycans; Reverse Transcriptase Polymerase Chain Reaction; Syndrome; Tendons

Glycosaminoglycan content, composition and molecular weight were determined in liver obtained from a patient with Morquio syndrome (Mucopolysaccharidosis IV). There was about a four-fold increase in glycosaminoglycan content (as hexosamine) of the affected liver as compared to the control liver. The major glycosaminoglycan accumulated in the liver was keratan sulfate, which was not found in the control liver. Chondroitin sulfates, especially chondroitin 6-sulfate, were also increased. Heparan sulfate isolated from the liver of a patient with Morquio syndrome was structurally different to that from control liver, and the glycosaminoglycans from Morquio syndrome were of a much lower molecular weight than those from control.

Topics: Adolescent; Child; Chondroitin Sulfates; Chromatography, Gel; Electrophoresis, Cellulose Acetate; Female; Glycosaminoglycans; Humans; Keratan Sulfate; Liver; Male; Molecular Weight; Mucopolysaccharidosis IV; Syndrome

Newer biochemical understanding of the mucopolysaccharidoses now allows a better classification of these diseases. The dermatan and keratan sulfate-storing diseases have corneal clouding. The heparan sulfate-storing diseases have retinal changes and usually central nervous system manifestations.

Topics: Child; Corneal Diseases; Dermatan Sulfate; Glycosaminoglycans; Heparitin Sulfate; Humans; Keratan Sulfate; Mucopolysaccharidoses; Syndrome

Chondro-osseous tissue from four patients with the Kniest dysplasia was studied histochemically using a new plastic embedding technique. Extensive vacuolar changes were observed p--1 throughout the endochondral growth plate and adjacent resting cartilage. These changes occurred within the cartilage matrix and also in the lacunae of degenerating chrondrocytes. The septa of the lesions contained chondroitin sulfate, but little keratan sulfate or collagen. Resting cartilage not adjacent to the growth plate stained irregularly and showed few of the vacuolar lesions, and chondrocytes were enlarged and contained cytoplasic inclusions, but no vacuolar material. Thus, there appears to be a sequence of events initiated by cellular accumulation of a substance and progressing to cellular and matrix degeneration.

Topics: Adolescent; Adult; Bone and Bones; Bone Diseases, Developmental; Cartilage; Cartilage Diseases; Child; Chondroitin Sulfates; Collagen; Female; Humans; Hypertrophy; Keratan Sulfate; Proteoglycans; Syndrome

The roentgenographic and clinical findings are described in a mother and daughter with the Kniest syndrome associated with urinary keratan sulfate excretion. Osteoporosis, kyphoscoliosis, vertebral irregularity, pelvic deformity, flat femoral heads and enlargement of the ends of the long bones were the main roentgen findings. Irregularity of ossification on both sides of the growth plate was observed in the daughter, and marked degenerative changes were superimposed on several of the mother's abnormal joints. Abnormal mucopolysacchariduria, observed in both patients, and cataracts, fusion of the symphysis pubis, and deficiency of carpal bones, seen in the mother, have not been described previously.

Topics: Adolescent; Adult; Bone and Bones; Bone Diseases, Developmental; Dwarfism; Female; Foot; Glycosaminoglycans; Hand; Humans; Keratan Sulfate; Mucopolysaccharidoses; Pelvis; Radiography; Syndrome; Wrist