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Bone manifestations in neuronopathic Gaucher disease while receiving high-dose enzyme replacement therapy
Kunal C Potnis1, Lauren B Flueckinger1, Christine I Ha1
1Division of Medical Genetics, Department of Pediatrics, Duke University Medical Center, Durham, NC, USA.
Molecular Genetics and Metabolism
|November 19, 2018
Summary
Avascular necrosis (AVN) can occur in Gaucher disease (GD) type 3 patients even with long-term enzyme replacement therapy (ERT). This highlights the need for musculoskeletal surveillance and novel treatments targeting bone marrow in GD.
Area of Science:
- Biochemistry
- Genetics
- Pediatrics
Background:
- Gaucher disease (GD) is a lysosomal storage disorder.
- Avascular necrosis (AVN) is a severe complication of GD, particularly type 3.
- The L483P variant (formerly L444P) is associated with severe GD phenotypes.
Observation:
- Two pediatric patients with GD type 3, homozygous for the L483P variant, developed AVN.
- AVN occurred despite long-term, high-dose enzyme replacement therapy (ERT) and normalized hematological/visceral parameters.
- Patients had intact spleens and received ERT shortly after diagnosis.
Findings:
- High-dose ERT did not prevent AVN in these GD patients.
- Bone marrow, a sanctuary site, may not be adequately targeted by ERT.
- Musculoskeletal surveillance is crucial in neuronopathic GD patients.
Implications:
- Current ERT may have limitations in preventing all GD complications.
- Novel therapeutic strategies targeting bone marrow are needed for GD.
- Regular monitoring of the skeletal system is essential for patients with GD type 3.
Keywords:
ACEAVNAvascular necrosisBMDBone manifestationsCHITODXAERTEnzyme replacement therapyGDGaucher diseaseMRIOsteonecrosisSRTTRAPangiotensin-converting enzymeavascular necrosisbone mineral densitychitotriosidasedual-energy X-ray absorptiometryenzyme replacement therapymagnetic resonance imagingsubstrate reduction therapytartrate-resistant acid phosphatase
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