Familial massive tendon xanthomatosis with decreased high-density lipoprotein-mediated cholesterol efflux

We experienced a family with novel massive tendon xanthomatosis which can be excluded from known disease causing xanthomatosis. The proband was a 58-year-old man who had necrosis in his massive Achilles tendon xanthoma. Three of 5 brothers including him and his nephew had the same clinical phenotype. The systemic tendon xanthomatosis became apparent around 30 years of their age. The proband and his elder brother had mild elevations of serum total cholesterol level (251 and 228 mg/dL, respectively). The low-density lipoprotein receptor activity of the proband's lymphocytes was normal. Neither plant sterol nor cholestanol level was increased in the proband's plasma. Magnetic resonance image of the proband's Achilles tendon demonstrated a massive expansion of the soft tissue with salami sausage-like appearance in his heels (50 mm in thickness). The physiological function of macrophages (MPhi) from the patients was investigated to clarify the mechanism for the formation of xanthomatosis. There was no significant difference in the uptake of oxidized low-density lipoprotein between the proband's MPhi and the control. High-density lipoprotein 3-mediated cholesterol efflux from the patients' MPhi (n = 2) was significantly reduced compared with the controls (n = 3), whereas there was no difference in apolipoprotein (apo) A-I-mediated cholesterol efflux between the patients' MPhi and the controls. Furthermore, there was no reduction of the messenger RNA levels of ATP-binding cassette transporter 1 (ABCA1), which is involved in apo A-I-mediated cholesterol efflux, in the proband's MPhi compared with the control. The present study demonstrates that the mechanism for the formation of novel familial massive tendon xanthomatosis may be, at least in part, associated with decreased high-density lipoprotein 3, but not free apo A-I-mediated cholesterol efflux from MPhi in vivo.