Journal of Inherited Metabolic Disease

, Volume 34, Issue 2, pp 429–437 | Cite as

Evaluation of high density lipoprotein as a circulating biomarker of Gaucher disease activity

  • Philip Stein
  • Ruhua Yang
  • Jun Liu
  • Gregory M. Pastores
  • Pramod K. Mistry
Rapid Communication


Circulating biomarkers are important surrogates for monitoring disease activity in type I Gaucher disease (GD1). We and others have reported low high-density lipoprotein (HDL) in GD1. We assessed HDL cholesterol as a biomarker of GD1, with respect to its correlation with indicators of disease severity and its response to imiglucerase enzyme replacement therapy (ERT). In 278 consecutively evaluated GD1 patients, we correlated HDL cholesterol, chitotriosidase, and angiotensin-converting enzyme (ACE) with indicators of disease severity. Additionally, we measured the response of these biomarkers to ERT. HDL cholesterol was negatively correlated with spleen volume, liver volume, and GD severity score index; the magnitude of this association of disease severity with HDL cholesterol was similar to that for ACE and for chitotriosidase. Within individual patients monitored over many years, there was a strikingly strong correlation of HDL with liver and spleen volumes; there was a similarly strong correlation of chitotriosidase and ACE with disease severity in individual patients monitored serially over many years (chitotriosidase r = 0.96 to 0.98, ACE r  = 0.88 to 0.94, and HDL r = −0.84 to −0.94, p < 0.001). ERT for 3 years resulted in a striking increase of HDL while serum levels of chitotriosidase and ACE decreased. Our results reveal markedly low HDL cholesterol in untreated GD1, a correlation with indicators of disease severity in GD1, and a rise towards normal after ERT. These findings suggest HDL cholesterol merits inclusion within the “biomarker basket” for monitoring of patients with GD1.


Enzyme Replacement Therapy Gauche Disease Familial Hypercholesterolemia Reverse Cholesterol Transport Spleen Volume 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



We are grateful to our patients for their participation in these studies. P.K.M. was supported by an NIDDK K24DK066306 Mid-Career Clinical Investigator award and an Investigator Initiated Study on Biomarker Discovery and Validation in Gaucher Disease by Genzyme Corporation. P.S. was supported by a Lysosomal Storage Fellowship Award from Genzyme Corporation.

Supplementary material

10545_2010_9271_MOESM1_ESM.pdf (16 kb)
Supplementary Table 1 (PDF 16 kb)
10545_2010_9271_MOESM2_ESM.pdf (21 kb)
Supplement Fig. 1 (PDF 21 kb)


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Copyright information

© SSIEM and Springer 2011

Authors and Affiliations

  • Philip Stein
    • 1
  • Ruhua Yang
    • 2
  • Jun Liu
    • 2
  • Gregory M. Pastores
    • 3
  • Pramod K. Mistry
    • 1
    • 2
    • 4
  1. 1.Department of Pediatrics, National Gaucher Disease Treatment CenterYale University School of MedicineNew HavenUSA
  2. 2.Department of Internal Medicine, National Gaucher Disease Treatment CenterYale University School of MedicineNew HavenUSA
  3. 3.NYU Department of Neurology, Neurogenetics UnitNew YorkUSA
  4. 4.Pediatric Gastroenterology and HepatologyYale University School of MedicineNew HavenUSA

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