EVIDENCE FOR MCKUSICKS HYPOTHESIS OF DEFICIENT COLLAGEN CROSS-LINKINGIN PATIENTS WITH HOMOCYSTINURIA

Osteoporosis occurs commonly in homocystinuria. The underlying pathobi ochemical mechanism remains unclear: disturbed cross-linking of collag en has been suggested but this hypothesis has not been fully tested, n or have studies on collagen synthesis been performed. We therefore use d recently available noninvasive tests for collagen synthesis and cros s-linking to examine 10 patients with homocystinuria. Synthesis of col lagen type I and type III was not different from age-matched healthy c ontrols as reflected by comparable plasma levels of carboxyterminal pr opeptide of type I procollagen (PICP) and of plasma levels of N-termin al propeptide of procollagen type III (PIIINP). Collagen type I cross- links expressed by serum carboxyterminal telopeptide of collagen type I (ICTP) were 1.14 +/- 0.23 mu g/l in the patient group versus 3.29 +/ - 0.32 mu g/l in the control group. This significant reduction of cros s-links in the group with homocystinuria did not correlate with serum homocysteine or homocysteic acid concentrations. Our data clearly indi cate that the disturbed cross-linking hypothesis still holds and that the bone manifestations of homocystinuria are not due to deficient col lagen synthesis.