Morphological and biochemical analysis of biopsy specimens in disorders of skeletal development

A programme for combined morphological and biochemical analysis of cartilage-bone biopsy material is described. The structural analysis includes light and electron microscopy, and the biochemistry is focused on polysaccharides. A procedure for isolation and characterization of proteoglycans and glycosaminoglycans from dry cartilage in amounts down to 1 mg is described. The procedure is exemplified by analyses of material from patients with osteogenesis imperfecta, mucopolysaccharidosis IV-Morquio and metaphyseal chondrodysplasia type McKusick. In osteogenesis imperfecta characteristic morphological alterations were demonstrated. Apart from increased chondroitin sulphate molecular weights, the biochemical analyses showed values within the assumed normal range. In Morquio's disease extensive intracellular deposits in single membrane vacuoles were observed in both chondrocytes and osteocytes. There were indications that these deposits contained keratan sulphate, which also occurred in increased amounts in the total tissue preparation. Furthermore, the tendency to formation of proteoglycan aggregates was decreased. In the tissue from the patients with the McKusick syndrome insignificant ultrastructural changes, mainly affecting the mitochondria, were found. The biochemical results were within the assumed normal range. The significance of these findings and the possibilities of further methodological development are discussed.