Disorder of collagen metabolism in a patient with osteogenesis imperfecta (lethal type): increased degree of hydroxylation of lysine in collagen types I and III

Abstract

Types I, II and III collagen were isolated from calvarium, skin and cartilage from a patient with recessive lethal osteogenesis imperfecta. The distribution of the various collagen types was normal in all three tissues. The α-chains were purified by molecular sieve and ion-exchange chromatography and were found to differ from the corresponding α-chains of age-matched controls only in that the α1(I), α2 and α1 (III) chains contained higher amounts of hydroxylysine with proportionally less lysine. α1(II) was normal. The excess hydroxylysine residues were all glycosylated in the case of α1(I) chains, but only partly so for the α2 chains. Similar observations were made with collagen from fetuses at various stages of development. In these fetuses, however, the increase in the degree of hydroxylation of lysine in αl(I), α2 and αl(III) varied with age, being highest in the youngest fetus. Seen in the context of embryonic development, the collagen of the patient would correspond to that of a fetus younger than 18 weeks, and one could speculate that the defect seen in this patient is the result of a disturbed process of maturation of connective tissue.