Case report and study of collagen metabolism in marfan's syndrome

Abstract

The case report on a 33 year old woman with prominent features of Marfan's syndrome is presented. Characteristic signs were seen in the bones, the eyes, the cardiovascular system, and the lungs. Due to regurgitation of both the aortic and mitral valves and an aneurysm of the ascending aorta a double valve replacement was made, including a prosthesis of the aorta. The problems of early diagnosis and therapy of the life-threatening cardiovascular complications are discussed. Tissue specimens from the aorta were analysed histochemically and biochemically. Histology showed a typical necrosis of the media with cyst formation. Biochemical analysis by in vitro labeling of collagen in tissue explants and by electron microscopical evaluation showed proportions of type I and type III collagen which were significantly different from controls. In both the media and the adventitia the amount of type I collagen was drastically reduced as shown by quantitation of collagen and procollagen. Fibroblasts derived from the skin of the patient showed a normal content of type I and type III collagen. It is conceivable that the reduced content of type I collagen in the aortic wall is responsible for the weakness of the vessel wall causing formation of aneurysm and its sequelae.

Marfan syndrome: Absence of type I or III collagen structural defects in 25 patients

“…In addition, we did not observe the slow electrophoretic migrations of collagen chains and peptides, resulting from overmodification of lysine residues, which have been observed with mutations of collagen c~chains in other genetically determined connective tissue diseases . Our finding of apparently normal type I and III collagen chains is in keeping with most of the biochemical studies which have been undertaken using dermis or cultured dermal fibroblasts from patients with the Marfan syndrome (Halbritter et al, 1981;Chemke et al, 1984;Muller et al, 1987). These findings are also in accordance with linkage studies of collagen restriction fragment length polymorphisms with the Marfan phenotype.…”

Zur Ultrastruktur kollagener Fibrillen in normalen und veränderten Blutgefässen

“…1976;Borojevic und Grimaud, 1980;Grimaud und Borojevic, 1980;Fischerei al., 1982] Mitralklappenerkrankung [Thiedeman und Ferraris, 1977] Pseudoxanthoma elasticum [Daroczy, 1980] Cutis laxa [ Marchase et al, 1980] Chronische Polyarthritis Tierexperimentelle Modelle Immunologisch induzierte Schädigung der Cornea; Kaninchen [Wagner, 1972] Ureterligatur; Ratte [Staubesand und Geister, 1980) fes [Fjolstad und Helle, 1974] [Scheck ei al., 1979;Byerset al, 1981]. An dere Arbeitsgruppen konnten diesen Defekt des Kollagenmoleküls jedoch nicht feststel len, dagegen einen Mangel an Typ-I-Kollagen [Halbritter et al, 1981].…”

Petros Tsipouras4

“…MS is a clinically heterogeneous group of genetic connective tissue disorders for which a clear understanding of their etiology has not yet emerged. Collagen structural genes are reasonable candidates for being the site of mutations resulting in MS. Biochemical evidence from two mutants indicated a structural defect in the proa2(1) collagen chain in one (Byers et al 1981), and a decrease of type I collagen in the aortic tissue in another (Halbritter et al 1981). Furthermore, defects in the proal(I), proa2(1), and proa l(II1) chains have been conclusively associated with different types of other connective tissue disorders such as osteogenesis imp&fecta and Ehler-Danlos Syndromes (Prockop & Kivirikko 1984).…”