keratan-sulfate and Dwarfism

Morquio disease is a rare genetic disorder characterized by the accumulation of keratan sulfate in tissues. We distinguish two forms according to the deficient enzyme: type A, with a poor prognosis, and type B. Its management is essentially symptomatic. Enzyme replacement therapy and gene therapy are still being evaluated. We report observations of three patients with Morquio disease type A in its moderate form. This article reports the latest facts in both Morquio disease diagnosis and treatment, emphasizing the minor forms usually presented by short stature that should bring out this disorder.

Topics: Biomarkers; Child; Consanguinity; Dwarfism; Female; Humans; Keratan Sulfate; Male; Mucopolysaccharidosis IV; Prognosis; Risk Factors; Severity of Illness Index

The brachymorphic (bm/bm) mouse is a disproportionate dwarf with a disturbance of the endochondral growth of the skeleton. Rib cartilage from 25-day-old affected animals and their normal siblings was analyzed for its contents and composition of proteoglycans. In addition to the previously reported undersulfation of chondroitin sulfate, it was demonstrated that one of the two types of aggregating proteoglycan and possibly the small ones are decreased in bm/bm costal cartilage, both in the growth region and in the remaining part. The molecular defect of the bm/bm condition is known to affect the synthesis of 3-phosphoadenosine 5-phosphosulfate (Sugahara and Schwartz, Proc. Natl. Acad. Sci. USA 76: 6615-6618, 1979). The above finding therefore suggests the existence of feedback mechanisms for the regulation of proteoglycan synthesis, whereby the undersulfation of glycosaminoglycans would result in decreased synthesis or increased turnover of certain proteoglycan subpopulations. Analysis of the glycosaminoglycan side chains indicated that mouse rib cartilage contains small amounts of keratan sulfate of extremely small size. The affected and control tissues, however, seemed to contain equal amounts of both glucosamine and galactosamine.

Topics: Animals; Cartilage; Chondroitin Sulfates; Dwarfism; Feedback; Glycosaminoglycans; Hexosamines; Keratan Sulfate; Mice; Mice, Mutant Strains; Molecular Weight; Phosphoadenosine Phosphosulfate; Proteoglycans; Rodent Diseases

Cartilage from patients with pseudoachondroplasia is characterized by unique inclusions in the cisternae of the endoplasmic reticulum and proteoglycan abnormalities have been suggested in this form of dwarfism. To elucidate the nature of the proteoglycan defect, we determined the amount of the individual glycosaminoglycans present in iliac-crest cartilage of three patients and extracted the proteoglycan monomers from one of the samples. Sections of iliac-crest cartilage and proximal fibular growth plates were examined by electron microscopy and also stained with hematoxylin and eosin, safranin O-fast green, and alcian blue in the presence of increasing concentrations of magnesium chloride (zero to one molar). The chondrocytes of the iliac crest and fibular physes were arranged in clusters more than in columns and contained characteristic endoplasmic reticulum inclusions, which were particularly large in the hypertrophic cells. The cartilage stained very poorly with hematoxylin and eosin and with safranin O-fast green. The alcian-blue stain was abolished from perilacunar areas and from longitudinal septa by magnesium chloride concentrations that were lower than those required by normal tissue. The proteoglycans of iliac-crest cartilage were found to be significantly enriched in keratan sulphate and had a below-normal ratio of chondroitin-4-sulphate to chondroitin-6-sulphate, although the amount of the two isomeric chondroitin sulphates combined was within normal limits. The urinary excretion of glycosaminoglycan by the three patients was normal. Pseudoachondroplasia appears to be a generalized cartilage disorder involving abnormalities of proteoglycans, probably related to the core protein or to enzymes that are responsible for the formation of the glycosaminoglycan chains.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Achondroplasia; Adolescent; Cartilage; Child; Chondroitin Sulfates; Dwarfism; Endoplasmic Reticulum; Glycosaminoglycans; Histocytochemistry; Humans; Keratan Sulfate; Proteoglycans

The clinical and radiological features of a patient with Kniest dysplasia, a form of metatropic dwarfism, are described. The patient excreted glycosaminoglycans (mucopolysaccharides) in normal amounts during infancy but subsequently showed abnormal keratan sulphate excretion. The significance of these findings and the possibility that Kniest dysplasia represent another mucopolysaccharidosis are discussed.

Topics: Abnormalities, Multiple; Clinical Laboratory Techniques; Dwarfism; Female; Glycosaminoglycans; Humans; Infant; Keratan Sulfate; Radiography

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