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High incidence of cholesterol gallstone disease in type 1 Gaucher disease: characterizing the biliary phenotype of type 1 Gaucher disease

  • Original Article
  • Published:
Journal of Inherited Metabolic 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 ∼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.

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Acknowledgements

NIH NIDDK T32DK007356 postdoctoral training program in investigative gastroenterology, the AASLD/ALF Sheila Sherlock Award, and the NIH CTSA/Yale Center for Clinical Investigation Scholar Award supported THT. NIDDK K24DK066306 midcareer clinical investigator award supported PKM. Yale Liver Center (Digestive Diseases Research Core Center) NIH NIDDK P30DK34989 (PI: J Boyer) and Howard Hughes Patient-Oriented Research pilot project grant (PI: RP Lifton) supported PKM for database development and genotyping and phenotyping studies. NIH DK48873 and DK56626 supported DEC. We thank the National Gaucher Foundation for their support and patients who participated in our studies. We thank Drs. James L Boyer and Martin C. Carey for critical discussions.

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Authors and Affiliations

  1. Department of Pediatrics, Yale School of Medicine, 333 Cedar Street, New Haven, CT, 06562, USA

    Ruhua Yang & Pramod K. Mistry

  2. Department of Medicine, Yale School of Medicine, 333 Cedar Street, New Haven, CT, 06562, USA

    Tamar H. Taddei & Pramod K. Mistry

  3. Department of Biostatistics, Yale School of Medicine, 333 Cedar Street, New Haven, CT, 06562, USA

    James Dziura & Shu Chen

  4. Department of Medicine and Molecular Science, Graduate School of Biomedical Sciences, Hiroshima University, Hiroshima, Japan

    Hideyuki Hyogo

  5. Bioanalytical Mass Spectrometry Facility, Georgia Institute of Technology, 315 Ferst Dr., Atlanta, GA, 30332-0363, USA

    Cameron Sullards

  6. Department of Medicine, Brigham and Women’s Hospital, 75 Francis Street, Boston, MA, USA

    David E. Cohen

  7. Neurogenetics Unit, NYU School of Medicine, New York, NY, USA

    Gregory Pastores

  8. Pediatric Hepatology and Gastroenterology, Yale School of Medicine, 333 Cedar Street, New Haven, CT, 06562, USA

    Pramod K. Mistry

Authors
  1. Tamar H. Taddei
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  2. James Dziura
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  4. Ruhua Yang
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  9. Pramod K. Mistry
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Corresponding author

Correspondence to Pramod K. Mistry.

Additional information

Communicated by: Robert Steiner

Competing interest: None declared.

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Taddei, T.H., Dziura, J., Chen, S. et al. High incidence of cholesterol gallstone disease in type 1 Gaucher disease: characterizing the biliary phenotype of type 1 Gaucher disease. J Inherit Metab Dis 33, 291–300 (2010). https://doi.org/10.1007/s10545-010-9070-1

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  • DOI: https://doi.org/10.1007/s10545-010-9070-1

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