title: Sitosterolemia presenting with severe hypercholesterolemia and intertriginous xanthomas in a breastfed infant: case report and brief review.
abstract: BACKGROUND
  Sitosterolemia is an autosomal recessive disorder characterized by increased intestinal absorption of plant sterols. It is caused by mutations in genes encoding ATP-binding cassette, subfamily G5 (ABCG5) or G8 (ABCG8), and clinical features include elevated plant sterol levels, xanthomas, and accelerated atherosclerosis. Although it was originally reported in patients with normolipemic xanthomas, patients with sitosterolemia also hyperabsorb cholesterol, and serum cholesterol levels tend to be elevated.
  
  
  OBJECTIVE
  We report an infant with sitosterolemia who presented with severe hypercholesterolemia and intertriginous xanthomas.
  
  
  METHODS
  A 15-month-old Korean girl presented with yellow dermal plaques over flexural areas including the wrist, neck, and gluteal folds, which were consistent with intertriginous xanthomas. The lesions were first noticed at 3 months of age when she was being exclusively breastfed. Her total cholesterol and low-density lipoprotein-cholesterol levels were 675 and 540 mg/dL, respectively. A low-fat/low-cholesterol diet and cholestyramine therapy were introduced. Unexpectedly, her serum cholesterol level decreased dramatically and normalized in 2 months. Cholestyramine was tapered off. The xanthomas also regressed and disappeared by 3 years of age. Gas chromatography-mass spectrometric analysis was performed with serum drawn at 3 years of age when her low-density lipoprotein-cholesterol was 118 mg/dL, which revealed striking elevation of her sitosterol level at 19.36 mg/dL. Direct sequencing for ABCG5 revealed compound heterozygous null mutations c.904+1G>A (p.Met302Asnfs*82) and c.1336C>T(p.Arg446*).
  
  
  CONCLUSIONS
  Our case suggests that sitosterolemia can present with severe hypercholesterolemia and intertriginous xanthomas. Sitosterolemia should be suspected when a patient with hypercholesterolemia shows unexpectedly good response to dietary modification or bile acid sequestrant therapy.
authors.affiliation: Departments of Pediatrics (J.H.P., I.H.C., E.-G.Y.) and Dermatology (D.H.K.), CHA University, Sungnam 463-712, Korea; Future Convergence Research Division (M.H.C.), Korea Institute of Science and Technology, Seoul 136-791, Korea; and Division of Nutrition and Metabolic Diseases (A.G.), Department of Internal Medicine, Center for Human Nutrition, UT Southwestern Medical Center, Dallas, Texas 75390.
authors.forename: Joong Heum
authors.initials: JH
authors.lastname: Park
authors.forename: In Hyuk
authors.initials: IH
authors.lastname: Chung
authors.forename: Dong Hyun
authors.initials: DH
authors.lastname: Kim
authors.forename: Man Ho
authors.initials: MH
authors.lastname: Choi
authors.forename: Abhimanyu
authors.initials: A
authors.lastname: Garg
authors.forename: Eun-Gyong
authors.initials: EG
authors.lastname: Yoo
mesh_terms: D000071018:ATP Binding Cassette Transporter, Subfamily G, Member 5; D018528:ATP-Binding Cassette Transporters / Q000235:genetics; D018752:Diet, Fat-Restricted; D005260:Female; D006801:Humans; D006937:Hypercholesterolemia / Q000175:diagnosis* / Q000178:diet therapy / Q000235:genetics; D007223:Infant; D007410:Intestinal Diseases / Q000175:diagnosis* / Q000178:diet therapy / Q000235:genetics; D008052:Lipid Metabolism, Inborn Errors / Q000175:diagnosis* / Q000178:diet therapy / Q000235:genetics; D008074:Lipoproteins / Q000235:genetics; D010840:Phytosterols / Q000009:adverse effects* / Q000235:genetics; D016896:Treatment Outcome; D014972:Xanthogranuloma, Juvenile / Q000175:diagnosis* / Q000178:diet therapy / Q000235:genetics
chemical_list: C416945:ABCG5 protein, human; D000071018:ATP Binding Cassette Transporter, Subfamily G, Member 5; D018528:ATP-Binding Cassette Transporters; D008074:Lipoproteins; D010840:Phytosterols