Gaucher Disease

1.Introduction8
2.Clinical aspects10
2.1.Classification10
2.1.1.Non-neuronopathic form of Gaucher disease10
2.1.2.Neuronopathic forms of Gaucher disease11
2.2.Definitions and history12
2.3.Aetiology and pathogenesis13
2.4.Epidemiology15
2.5.Natural course and prognosis16
2.6.Classification of severity18
3.Diagnostics22
3.1.General symptoms22
3.2.Medical history and clinical findings22
3.3.Laboratory24
3.4.Diagnostic procedures25
3.5.Acute neuronopathic form (infantile form, type 2)27
3.6.Enzyme measurement28
3.7.Molecular genetic diagnosis29
3.8.Bone manifestations in Gaucher disease30
3.8.1.Introduction30
3.8.2.Pathophysiology and clinical complications of bone disease30
3.8.2.1.Skeletal complications in Gaucher disease30
3.8.2.2.Bone mineralisation and osteoclast activity in Gaucher disease36
3.8.2.3.Variability of bone complications in patients with Gaucher disease36
3.8.2.4.The impact of the disease in patients with skeletal pathology37
3.8.2.5.Skeletal pathology in children with Gaucher disease38
3.8.3.Assessment and monitoring of skeletal pathology38
3.8.3.1.Qualitative imaging procedures38
3.8.3.2.Quantitative imaging procedures39
3.8.3.3.Semiquantitative staging and classification systems40
3.8.3.4.Assessment of skeletal pathology41
3.8.4.Therapy of skeletal pathology42
3.8.4.1.Response of the skeleton to enzyme replacement therapy - clinical data42
3.8.4.2.Reconversion of the yellow bone marrow44
3.8.5.Conclusions44
4.Therapy48
4.1.Enzyme replacement therapy48
4.1.1.Historical aspects48
4.1.2.Non-neuronopathic Gaucher disease (previously known as type 1)50
4.1.2.1.Quality of life50
4.1.2.2.Haematological findings52
4.1.2.3.Hepatosplenomegaly52
4.1.2.4.Bone changes52
4.1.2.5.Lung involvement53
4.1.3.Acute neuronopathic Gaucher disease (previously known as type 2)55
4.1.4.Chronic neuronopathic course (previously known as type 3)55
4.1.5.Special considerations for children56
4.1.6.Dose finding58
4.1.7.Therapy monitoring62
4.1.8.Side effects of enzyme replacement therapy65
4.1.9.Enzyme replacement therapy and pregnancy65
4.2.Small molecules66
4.2.1.Substrate reduction66
4.2.1.1.Miglustat66
4.2.1.2.Genz-11263868
4.2.2.Chaperones68
4.3.Comparison of the effect of enzyme replacement therapy (Cerezyme®) and substrate
inhibition (miglustat)70
4.4.Gene Therapy71
4.5.Concomitant therapy72
5.Gaucher Registry76
6.Patient self-help groups80
Index86