Eugen Mengel

Niemann-Pick disease (eBook, PDF)

• Format: PDF

Produktbeschreibung

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.

Produktdetails

• Verlag: UNI-MED Verlag AG
• Seitenzahl: 87
• Erscheinungstermin: 16. November 2022
• Englisch
• ISBN-13: 9783837464474
• Artikelnr.: 66435769

Inhaltsangabe

1.Historical aspects of Niemann-Pick disease12 2.Biochemistry of Niemann-Pick disease18 2.1.Introduction and definitions18 2.2.Missing or pathological products of “Niemann-Pick genes“19 2.3.Biochemical foundations of diagnosing Niemann-Pick diseases 19 2.3.1.Niemann-Pick disease, SMPD1-associated19 2.3.2.Niemann-Pick disease, transport protein deficiency-associated (NPC1, NPC2)19 2.3.3.Chitotriosidase activity in plasma20 2.3.4.Determination of oxysterols20 2.3.5.Determination of lyso-sphingomyelin-509 (lyso-SM-509)21 2.3.6.Determination of bile acids21 2.4.Biochemistry of Niemann-Pick diseases that is pathogenetically relevant or suspected to be significant21 2.4.1.Niemann-Pick disease, SMPD1-associated21 2.4.2.Niemann-Pick disease, transport protein deficiency-associated (NPC1, NPC2) in general22 2.4.3.Niemann-Pick disease, transport protein deficiency-associated (NPC1, NPC2), central nervous system24 2.5.Animal models25 2.5.1.Niemann-Pick disease, SMPD1-associated25 2.5.2.Niemann-Pick disease, transport protein deficiency-associated (NPC1, NPC2)25 2.6.Therapeutic concepts for the possible influence of pathogenetically significant metabolic changes26 2.6.1.Niemann-Pick disease, SMPD1-associated26 2.6.2.Niemann-Pick disease, transport protein deficiency-associated (NPC1)26 3.Genetics of Niemann-Pick disease34 3.1.Niemann-Pick disease type A/B (NPA/B) [MIM: 257200/607616]34 3.1.1.SMPD1 gene and ASM protein [HGNC Gene-ID: 11120]34 3.1.2.SMPD1 variants34 3.2.Niemann-Pick disease type C (NPC) [MIM: 257220/607625]35 3.2.1.NPC1 gene and protein [HGNC Gene-ID: 7897]36 3.2.2.NPC1 variants37 3.2.3.NPC2 gene and protein [HGNC Gene-ID: 14537]38 3.2.4.NPC2 variants38 3.3.Challenges of genetic testing in Niemann-Pick disease and outlook38 3.4.Genetic databases for Niemann-Pick diseases39 4.Diagnosis of Niemann-Pick disease type C (NPC) 44 4.1.Recommendations for differential diagnosis and initial diagnosis44 4.2.Clinical diagnosis and key findings in NPC46 4.2.1.Neuropsychological diagnosis and key findings46 4.2.2.Laboratory diagnostics and biomarkers47 4.3.Significance of genetic testing in NPC50 4.3.1.Next-generation sequencing (NGS) and gene panels52 4.3.2.Differentiation from acid sphingomyelinase deficiency (ASMD)52 4.4.Differential diagnosis of similar lysosomal diseases54 5.Clinical manifestation58 5.1.Niemann-Pick disease type A and type B58 5.2.Niemann-Pick type C disease62 5.2.1.Perinatal type63 5.2.2.Infantile type64 5.2.3.Late-infantile type64 5.2.4.Juvenile classic type67 5.2.5.Adult type70 5.2.6.Psychiatric manifestations in Niemann-Pick type C disease71 6.Management and treatment of Niemann-Pick diseases80 6.1.Management and treatment of Niemann-Pick type A/B disease80 6.1.1.Supportive care80 6.1.2.Causal therapeutic approaches81 6.1.3.Future therapy options82 6.2.Management and treatment of Niemann-Pick type C disease83 6.2.1.Miglustat84 6.2.2.Bone marrow and liver transplantations85 6.2.3.Treatment of extrapyramidal symptoms, spasticity, cataplexy and epilepsy85 6.2.4.Substances in preclinical and experimental studies86 Index87

---

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 findings464.2.2.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