title: A family of familial hypercholesterolemia with cerebral infarction and without coronary heart disease. An unusual case with corneal opacity, polyneuropathy and carpal tunnel syndrome in the family: therapy with probucol and tocopherol nicotinate.
abstract: A study is presented of a 48-year-old female patient and her three siblings with familial hypercholesterolemia. The family members had episodes of cerebral infarction and apparently had atherosclerosis of the internal carotid artery, but no coronary heart disease due to their almost normal level of cholesterol. The laboratory studies of the family members revealed the elevations of serum lipid peroxides, serum lipoprotein(a), leukotriene C4 in blood, the thromboxane B2/6-keto-prostaglandin F1 alpha ratio in plasma and serum hydroxyl radical. Therefore, it is suspected that these factors accelerating atherosclerotic process caused the cerebral infarction. The patient demonstrated corneal opacities, palpebral xanthomas, thickened Achilles tendons, polyneuropathy and the carpal tunnel syndrome. Laboratory studies revealed an elevation in the OKT4/8 ratio, monocyte dysfunction with respect to phagocytosis and chemotaxis, and the presence of the 46XX/45XO mosaic chromosome. Lipid deposits were observed in the Achilles tendon, the transverse carpal ligament, the Schwann's cells and axons of the sural nerve, and in the keratocytes and stroma of the cornea. Following the administration of tocopherol nicotinate and probucol, the patient's serum lipid peroxide normalized and there was improvement in her palpebral xanthomas, thickening of the Achilles tendons and polyneuropathy. We conclude that the lipid deposits in this patient were due to the abnormal oxidative metabolism of low-density lipoprotein and a disturbance of the scavenger pathway due to the monocyte dysfunction.
authors.affiliation: Department of Neurology, National Minamiokayama Hospital, Okayama, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Ihara
authors.forename: K
authors.initials: K
authors.lastname: Nobukuni
authors.forename: R
authors.initials: R
authors.lastname: Namba
authors.forename: K
authors.initials: K
authors.lastname: Kamisaka
authors.forename: M
authors.initials: M
authors.lastname: Kibata
authors.forename: K
authors.initials: K
authors.lastname: Kajinami
authors.forename: H
authors.initials: H
authors.lastname: Fujita
authors.forename: H
authors.initials: H
authors.lastname: Mabuchi
authors.forename: T
authors.initials: T
authors.lastname: Shirabe
authors.forename: K
authors.initials: K
authors.lastname: Ohshima
mesh_terms: D001161:Arteriosclerosis / Q000235:genetics; D001369:Axons / Q000473:pathology; D016516:CD4-CD8 Ratio; D002349:Carpal Tunnel Syndrome / Q000235:genetics; D002544:Cerebral Infarction / Q000235:genetics*; D003318:Corneal Opacity / Q000235:genetics; D005260:Female; D005609:Free Radicals; D015417:Hereditary Sensory and Motor Neuropathy / Q000235:genetics*; D006801:Humans; D006938:Hyperlipoproteinemia Type II / Q000097:blood / Q000188:drug therapy / Q000235:genetics*; D008077:Lipoproteins, LDL / Q000097:blood; D008875:Middle Aged; D009030:Mosaicism; D009539:Nicotinic Acids / Q000627:therapeutic use; D011341:Probucol / Q000627:therapeutic use; D012583:Schwann Cells / Q000473:pathology; D013482:Superoxide Dismutase / Q000097:blood; D014424:Turner Syndrome / Q000235:genetics; D014810:Vitamin E / Q000031:analogs & derivatives / Q000627:therapeutic use
chemical_list: D005609:Free Radicals; D008077:Lipoproteins, LDL; D009539:Nicotinic Acids; D014810:Vitamin E; C012581:alpha-tocopheryl nicotinate; D013482:Superoxide Dismutase; D011341:Probucol