title: Evidence for McKusick's hypothesis of deficient collagen cross-linking in patients with homocystinuria.
abstract: Osteoporosis occurs commonly in homocystinuria. The underlying pathobiochemical mechanism remains unclear; disturbed cross-linking of collagen has been suggested but this hypothesis has not been fully tested, nor have studies on collagen synthesis been performed. We therefore used recently available noninvasive tests for collagen synthesis and cross-linking to examine 10 patients with homocystinuria. Synthesis of collagen type I and type III was not different from age-matched healthy controls as reflected by comparable plasma levels of carboxyterminal propeptide of type I procollagen (PICP) and of plasma levels of N-terminal propeptide of procollagen type III (PIIINP). Collagen type I cross-links expressed by serum carboxyterminal telopeptide of collagen type I (ICTP) were 1.14 +/- 0.24 micrograms/l in the patient group versus 3.29 +/- 0.32 micrograms/l in the control group. This significant reduction of cross-links in the group with homocystinuria did not correlate with serum homocysteine or homocysteic acid concentrations. Our data clearly indicate that the disturbed cross-linking hypothesis still holds and that the bone manifestations of homocystinuria are not due to deficient collagen synthesis.
authors.affiliation: University of Vienna, Department of Paediatrics, Austria.
authors.forename: B
authors.initials: B
authors.lastname: Lubec
authors.forename: S
authors.initials: S
authors.lastname: Fang-Kircher
authors.forename: T
authors.initials: T
authors.lastname: Lubec
authors.forename: H J
authors.initials: HJ
authors.lastname: Blom
authors.forename: G H
authors.initials: GH
authors.lastname: Boers
mesh_terms: D000328:Adult; D015415:Biomarkers; D002648:Child; D002675:Child, Preschool; D003094:Collagen / Q000097:blood* / Q000737:chemistry / Q000378:metabolism*; D024042:Collagen Type I; D003541:Cystathionine beta-Synthase / Q000172:deficiency / Q000235:genetics; D005260:Female; D006710:Homocysteine / Q000097:blood; D006712:Homocystinuria / Q000145:classification / Q000150:complications / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008297:Male; D042965:Methylenetetrahydrofolate Reductase (NADPH2); D008875:Middle Aged; D008954:Models, Biological; D010024:Osteoporosis / Q000209:etiology / Q000378:metabolism; D000587:Oxidoreductases Acting on CH-NH Group Donors / Q000172:deficiency / Q000235:genetics; D010446:Peptide Fragments / Q000097:blood*; D010455:Peptides / Q000097:blood*; D011347:Procollagen / Q000097:blood* / Q000378:metabolism; D011499:Protein Processing, Post-Translational; D012995:Solubility
chemical_list: D015415:Biomarkers; D024042:Collagen Type I; D010446:Peptide Fragments; D010455:Peptides; D011347:Procollagen; C052929:collagen type I trimeric cross-linked peptide; C041876:procollagen Type III-N-terminal peptide; C042813:procollagen type I carboxy terminal peptide; D006710:Homocysteine; D003094:Collagen; D000587:Oxidoreductases Acting on CH-NH Group Donors; D042965:Methylenetetrahydrofolate Reductase (NADPH2); D003541:Cystathionine beta-Synthase