Niemann-Pick disease

Sphingomyelinase deficiency Niemann-Pick type A & B disease and intracellular lipid transport defect Niemann-Pick type C disease are to be considered as two genetically and molecularly distinct entities.This book is devoted to these two disorders and comprehensively presents the diagnostic options, including how to distinguish between Niemann-Pick type A & B and type C, as well as current therapeutic approaches. It also considers molecular biology, the latest findings in the field of basic science, and the current understanding of clinical features. A separate chapter on diagnosis can be used as a quick reference work from clinical symptoms to a suspected diagnosis and the confirmation of diagnosis in the laboratory.

Inhaltsverzeichnis:

1.Historical aspects of Niemann-Pick disease122.Biochemistry of Niemann-Pick disease182.1.Introduction and definitions182.2.Missing or pathological products of "Niemann-Pick genes"192.3.Biochemical foundations of diagnosing Niemann-Pick diseases 192.3.1.Niemann-Pick disease, SMPD1-associated192.3.2.Niemann-Pick disease, transport protein deficiency-associated (NPC1, NPC2)192.3.3.Chitotriosidase activity in plasma202.3.4.Determination of oxysterols202.3.5.Determination of lyso-sphingomyelin-509 (lyso-SM-509)212.3.6.Determination of bile acids212.4.Biochemistry of Niemann-Pick diseases that is pathogenetically relevant or suspected to be significant212.4.1.Niemann-Pick disease, SMPD1-associated212.4.2.Niemann-Pick disease, transport protein deficiency-associated (NPC1, NPC2) in general222.4.3.Niemann-Pick disease, transport protein deficiency-associated (NPC1, NPC2), central nervous system242.5.Animal models252.5.1.Niemann-Pick disease, SMPD1-associated252.5.2.Niemann-Pick disease, transport protein deficiency-associated (NPC1, NPC2)252.6.Therapeutic concepts for the possible influence of pathogenetically significant metabolic changes262.6.1.Niemann-Pick disease, SMPD1-associated262.6.2.Niemann-Pick disease, transport protein deficiency-associated (NPC1)263.Genetics of Niemann-Pick disease343.1.Niemann-Pick disease type A/B (NPA/B) [MIM: 257200/607616]343.1.1.SMPD1 gene and ASM protein [HGNC Gene-ID: 11120]343.1.2.SMPD1 variants343.2.Niemann-Pick disease type C (NPC) [MIM: 257220/607625]353.2.1.NPC1 gene and protein [HGNC Gene-ID: 7897]363.2.2.NPC1 variants373.2.3.NPC2 gene and protein [HGNC Gene-ID: 14537]383.2.4.NPC2 variants383.3.Challenges of genetic testing in Niemann-Pick disease and outlook383.4.Genetic databases for Niemann-Pick diseases394.Diagnosis of Niemann-Pick disease type C (NPC) 444.1.Recommendations for differential diagnosis and initial diagnosis444.2.Clinical diagnosis and key findings in NPC464.2.1.Neuropsychological diagnosis and key fi ndings464.2.2.Laboratory diagnostics and biomarkers474.3.Significance of genetic testing in NPC504.3.1.Next-generation sequencing (NGS) and gene panels524.3.2.Differentiation from acid sphingomyelinase deficiency (ASMD)524.4.Differential diagnosis of similar lysosomal diseases545.Clinical manifestation585.1.Niemann-Pick disease type A and type B585.2.Niemann-Pick type C disease625.2.1.Perinatal type635.2.2.Infantile type645.2.3.Late-infantile type645.2.4.Juvenile classic type675.2.5.Adult type705.2.6.Psychiatric manifestations in Niemann-Pick type C disease716.Management and treatment of Niemann-Pick diseases806.1.Management and treatment of Niemann-Pick type A/B disease806.1.1.Supportive care806.1.2.Causal therapeutic approaches816.1.3.Future therapy options826.2.Management and treatment of Niemann-Pick type C disease836.2.1.Miglustat846.2.2.Bone marrow and liver transplantations856.2.3.Treatment of extrapyramidal symptoms, spasticity, cataplexy and epilepsy856.2.4.Substances in preclinical and experimental studies86Index87