Case Report
Impact on bone microarchitecture and failure load in a patient with type I Gaucher disease who switched from Imiglucerase to Eliglustat

https://doi.org/10.1016/j.ymgmr.2020.100606Get rights and content
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Abstract

Gaucher disease (GD; OMIM 230800) is a lysosomal storage disorder caused by a deficiency in acid beta-glucosidase as a result of mutation in the GBA gene. Type 1 GD (GD1) is the most common form and its clinical manifestations include severe hematological, visceral and bone disease. The goal of disease-modifying treatments for GD1 is to reduce substrate storage and hence toxicity from the disease. The two common therapeutic routes for managing GD1 are enzyme replacement therapy (ERT) and substrate reduction therapy (SRT). These therapies have shown to improve hematological and visceral aspects of the disease. However, quantitative investigations into how these therapies may help prevent or improve the progression of bone disease is limited. This case involves a patient diagnosed with GD1 in childhood, who began ERT in young adulthood. Following over 20 years of treatment with ERT, the patient switched to SRT. This case report examined the novel application of high-resolution peripheral quantitative computed tomography (HR-pQCT) in a patient who switched from ERT to SRT. Using bone microarchitecture measurements from HR-pQCT, we applied finite element analysis techniques to calculate the failure load which estimates the resistance to fracture. Over the course of one year following the switch from ERT to SRT therapy, failure load improved in the patient's lower limb. In conclusion, failure load can be computed in the short term in a patient who made a switch from ERT to SRT. Further exploration of failure load in study design to look at interventions that impact bone quality in GD may be considered.

Keywords

Gaucher disease
Bone disease
High-resolution peripheral quantitative computed tomography
Finite element analysis
Enzyme replacement therapy
Substrate replacement therapy

Abbreviations

GD
Gaucher Disease
GD1
Gaucher Disease (type I)
ICGG
International Collaborative Gaucher Group
DXA
Dual-energy x-ray absorptiometry
HR-pQCT
High-resolution peripheral quantitative computed tomography
MRI
Magnetic resonance imaging
BMD
Bone mineral density
ERT
Enzyme replacement therapy
SRT
Substrate reduction therapy
LS
Lumbar spine
FN
Femoral neck
LSC
Least significant change

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