title: High incidence of cholesterol gallstone disease in type 1 Gaucher disease: characterizing the biliary phenotype of type 1 Gaucher disease.
abstract: BACKGROUND
  In Gaucher disease (GD), lysosomal glucocerebrosidase deficiency results in glucosylceramide accumulation in macrophage lysosomes. Hepatocytes do not accumulate glucosylceramide due in part to biliary secretion. Although gallstones (GS) occur in type 1 Gaucher disease (GD1), the chemical nature of stones, their association with metabolic parameters, and whether bile composition is altered are not understood. We assessed the prevalence of GS, their chemical composition, biliary lipids, and associated metabolic factors.
  
  
  METHODS
  The study cohort comprised 417 patients comprehensively evaluated for GD1 severity. Ascertainment of GS, fasting lipoprotein profile, and bile lipid analyses were performed.
  
  
  RESULTS
  The prevalence of GS in GD1 was 32%. Compared with men, the prevalence of GS was higher in women, increasing from 4.2% and 11.8% at age 20-29 years to 71% and 60% at age >70 years, respectively. Patients with GS were more likely to be asplenic (p < 0.0001), older (p < 0.0001), have higher low-density lipoprotein (LDL) cholesterol (p = 0.002), and more severe GD1 disease compared with those without GS. On multiple logistic regression analysis, factors associated with GS were age (p < 0.001), female sex (p = 0.03), and splenectomy (p = 0.005). Compared with the general population, prevalence of GS was approximately 5-fold higher. Bile lipid analyses revealed cholesterol stones in five patients and pigment stones in one. Bile lipid composition was abnormal and contained glucosylceramide.
  
  
  CONCLUSIONS
  Our results point to a metabolic syndrome in GD1 consisting of a propensity to cholesterol GS, low high-density lipoprotein (HDL) cholesterol, LDL cholesterol, and body mass index (BMI) associated with abnormal biliary lipid secretion.
authors.affiliation: Department of Medicine, Yale School of Medicine, New Haven, CT 06562, USA.
authors.forename: Tamar H
authors.initials: TH
authors.lastname: Taddei
authors.forename: James
authors.initials: J
authors.lastname: Dziura
authors.forename: Shu
authors.initials: S
authors.lastname: Chen
authors.forename: Ruhua
authors.initials: R
authors.lastname: Yang
authors.forename: Hideyuki
authors.initials: H
authors.lastname: Hyogo
authors.forename: Cameron
authors.initials: C
authors.lastname: Sullards
authors.forename: David E
authors.initials: DE
authors.lastname: Cohen
authors.forename: Gregory
authors.initials: G
authors.lastname: Pastores
authors.forename: Pramod K
authors.initials: PK
authors.lastname: Mistry
mesh_terms: D000328:Adult; D015992:Body Mass Index; D002769:Cholelithiasis / Q000150:complications* / Q000175:diagnosis* / Q000453:epidemiology / Q000473:pathology; D002784:Cholesterol / Q000378:metabolism*; D008078:Cholesterol, LDL / Q000378:metabolism; D015331:Cohort Studies; D005260:Female; D005776:Gaucher Disease / Q000150:complications* / Q000175:diagnosis* / Q000453:epidemiology; D005963:Glucosylceramides / Q000378:metabolism; D022781:Hepatocytes / Q000378:metabolism; D006801:Humans; D015994:Incidence; D008247:Lysosomes / Q000378:metabolism; D008264:Macrophages / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D008954:Models, Biological; D010641:Phenotype; D015995:Prevalence
chemical_list: D008078:Cholesterol, LDL; D005963:Glucosylceramides; D002784:Cholesterol