Document Detail


High incidence of cholesterol gallstone disease in type 1 Gaucher disease: characterizing the biliary phenotype of type 1 Gaucher disease.
MedLine Citation:
PMID:  20354791     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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:
Tamar H Taddei; James Dziura; Shu Chen; Ruhua Yang; Hideyuki Hyogo; Cameron Sullards; David E Cohen; Gregory Pastores; Pramod K Mistry
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2010-03-31
Journal Detail:
Title:  Journal of inherited metabolic disease     Volume:  33     ISSN:  1573-2665     ISO Abbreviation:  J. Inherit. Metab. Dis.     Publication Date:  2010 Jun 
Date Detail:
Created Date:  2010-05-27     Completed Date:  2010-09-28     Revised Date:  2011-04-15    
Medline Journal Info:
Nlm Unique ID:  7910918     Medline TA:  J Inherit Metab Dis     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  291-300     Citation Subset:  IM    
Affiliation:
Department of Medicine, Yale School of Medicine, New Haven, CT 06562, USA.
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MeSH Terms
Descriptor/Qualifier:
Adult
Body Mass Index
Cholelithiasis / complications*,  diagnosis*,  epidemiology,  pathology
Cholesterol / metabolism*
Cholesterol, LDL / metabolism
Cohort Studies
Female
Gaucher Disease / complications*,  diagnosis*,  epidemiology
Glucosylceramides / metabolism
Hepatocytes / metabolism
Humans
Incidence
Lysosomes / metabolism
Macrophages / metabolism
Male
Middle Aged
Models, Biological
Phenotype
Prevalence
Grant Support
ID/Acronym/Agency:
DK48873/DK/NIDDK NIH HHS; DK56626/DK/NIDDK NIH HHS; K24 DK066306-01A2/DK/NIDDK NIH HHS; K24DK066306/DK/NIDDK NIH HHS; P30 DK034989-16/DK/NIDDK NIH HHS; P30DK34989/DK/NIDDK NIH HHS; R01 DK048873-07A1/DK/NIDDK NIH HHS; R01 DK048873-16/DK/NIDDK NIH HHS; R01 DK056626-01A1/DK/NIDDK NIH HHS; T32 DK007356-26/DK/NIDDK NIH HHS; T32DK007356/DK/NIDDK NIH HHS; //Howard Hughes Medical Institute; //Howard Hughes Medical Institute
Chemical
Reg. No./Substance:
0/Cholesterol, LDL; 0/Glucosylceramides; 57-88-5/Cholesterol

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