Handbook of Porphyrin Science (Volume 29)

The following sections are included:

• Contents

• Preface for Volumes 26–30

• Preface for Volumes 21–25

• Contributing Authors for Volumes 1–30

• Contents of Volumes 1–30

The following sections are included:

• List of Abbreviations

• Introduction

• Heme Biosynthesis — An Overview

• Porphyrias — An Overview

• Two Routes to ALA
  • Shemin Pathway
  • “C₅-Pathway” for ALA Formation

• UROGEN Formation from ALA
  • Porphobilinogen Synthase
  • Porphobilinogen Deaminase
  • Uroporphyrinogen III Synthase

• Conversion of UROGEN into Heme
  • Uroporphyrinogen III Decarboxylase
  • Coproporphyrinogen III Oxidase
  • Coproporphyrinogen III Dehydrogenase
  • Protoporphyrinogen IX Oxidase
  • Ferrochelatase

• Acknowledgments

• References

The following sections are included:

• List of Abbreviations

• Introduction
  • Historical Aspects
  • Definition of Sideroblastic Anemia
  • Classification of Sideroblastic Anemias

• Central Roles of the Mitochondrion in the Pathogenesis of Sideroblastic Anemias
  • Heme Biosynthesis in the Erythroid Cell
  • Biogenesis of Fe–S Clusters
  • Mitochondrial Protein Synthesis
  • Iron Homeostasis in the Erythroid Cell

• Congenital Sideroblastic Anemias
  • X-Linked Sideroblastic Anemia
  • Autosomal Recessive Sideroblastic Anemias
  • Undefined Category of Congenital Sideroblastic Anemia(s)

• Syndromic Forms of Congenital Sideroblastic Anemia
  • X-Linked Sideroblastic Anemia with Ataxia
  • Myopathy, Lactic Acidosis, and Sideroblastic Anemia
  • Congenital Sideroblastic Anemia, B Cell Immunodeficiency, Periodic Fevers, and Developmental Delay
  • Pearson Marrow-pancreas Syndrome
  • Thiamine Responsive Megaloblastic Anemia

• Acquired Clonal Sideroblastic Anemia
  • Pathogenesis
  • Clinical Features
  • Treatment and Prognosis

• Acquired Reversible Sideroblastic Anemias
  • Alcoholism
  • Drug-induced Sideroblastic Anemia
  • Copper Deficiency
  • Hypothermia

• Summary and Future Prospects

• Acknowledgments

• References

The following sections are included:

• List of Abbreviations

• Introduction

• Heme Biosynthesis
  • Structure of Porphyrins
  • Synthesis of Porphyrin Precursors: δ-ALA and PBG
  • Synthesis of Coproporphyrinogen III
  • Synthesis of Heme

• Excretion of Porphyrin Precursors and Porphyrins
  • Porphyrin Precursors and Porphyrins in Urine
  • Porphyrin Precursors and Porphyrins in Feces

• Heme Catabolism

• Regulation of Heme Synthesis
  • In the Liver
  • In Erythroid Cells

• Pathogenesis of an Acute Attack

• Pathogenesis of Skin Injury

• Conclusions and Future Directions

• References

The following sections are included:

• List of Abbreviations

• Introduction

• Definitions

• Prevalence of Porphyrias

• Autosomal Dominant Acute Porphyrias
  • Molecular Genetics
  • Demography
  • Prevalence and Incidence
  • Penetrance

• Porphyria Cutanea Tarda
  • Molecular Genetics of PCTF
  • Demography
  • Prevalence and Incidence
  • Susceptibility Factors

• Erythropoietic Protoporphyria
  • Molecular Genetics
  • Demography
  • Prevalence and Incidence

• Conclusion

• References

The following sections are included:

• List of Abbreviations

• Introduction

• History

• Core Defect in CEP

• Accumulation of Porphyrins

• Clinical Features of CEP
  • Hematological Features
  • Cutaneous Manifestations
  • Pathogenesis of Skin Lesions
  • Ocular Involvement
  • Erythrodontia
  • Skeletal Abnormalities
  • Progression of the Disease
  • Association with Other Diseases
  • Autopsy Reports
  • Mild Cases
  • Late-onset Cases
  • Prenatal Manifestations of Severe Cases
  • Neonatal Period

• Diagnosis

• CEP in Animals

• URO Synthase Gene

• Mutations Causing CEP
  • Mutations in the URO Synthase Gene
  • Trans-acting Mutations Causing CEP
  • Frequency of the URO Synthase Mutations

• Relationship between the Genotype and the Clinical Phenotype
  • Homozygous Patients
  • Compound Heterozygous Patients
  • Modifier Genes in CEP
  • Mixed Phenotypes

• Murine Models of CEP

• URO Synthase Structure and Function
  • URO Synthase High-Resolution Structures
  • Substrate-binding Site and URO Synthase Catalytic Mechanism
  • Mapping of Missense Mutations in URO Synthase
  • Stability and Catalytic Activity of CEP-associated URO Synthase Variants
  • Structural Rescue of Deficient URO Synthase Activity

• Treatment of CEP
  • Miscellaneous
  • Hematopoietic Stem Cell Transplantation
  • Experimental Gene Therapy

• Conclusions and Future Directions

• Acknowledgments

• References

The following sections are included:

• List of Abbreviations

• Introduction

• History and Nomenclature

• Human Uroporphyrinogen Decarboxylase
  • UROD Locus
  • UROD Activity
  • Molecular Pathology and UROD Deficiency Classification

• Pathogenesis
  • Experimental Uroporphyria
  • Iron Overload
  • Cytochrome P4501A2 Induction and Polymorphisms
  • UROD Inhibition
  • Susceptibility Factors

• Prevalence

• Clinical Features
  • Skin Lesions
  • Liver Disease

• Diagnosis
  • History and Physical Examination
  • Laboratory Diagnosis
  • Differential Diagnosis

• Treatment
  • General Measures
  • Specific Treatment
  • Genetic Counseling

• Natural History and Prognosis

• Summary and Conclusions

• Acknowledgments

• References

The following sections are included:

• List of Abbreviations

• Introduction

• History and Prevalence
  • History
  • Occurrence

• Heme Biosynthetic Enzymes in VP
  • Primary Enzymatic Defect in VP
  • ALA Synthase and PBG Deaminase in VP

• PPOX Gene

• PPOX Reaction

• PPOX Gene Product
  • PPOX Structure

• PPOX Mutations

• Effects of Mutations in PPOX
  • PPOX Activity
  • PPOX Structure

• Porphyrin Production and Excretion in VP

• Diagnosis of VP
  • Laboratory Diagnosis

• Clinical Features of VP
  • Skin Disease
  • Treatment
  • Acute Attack
  • Precipitants of the Acute Attack
  • Treatment of the Acute Attack
  • Supportive Care
  • Penetrance
  • Homozygous VP

• Final Comment and Future Directions

• Acknowledgments

• References

The following sections are included:

• List of Abbreviations

• Introduction

• Prevalence and Epidemiology

• Clinical Features
  • Photosensitivity
  • Hematologic Abnormalities
  • Iron Metabolism in EPP
  • Liver Involvement
  • Late Onset EPP

• Laboratory Findings
  • Plasma Fluorescence Scanning
  • Fecal Protoporphyrin Content
  • Zinc and Metal-free Protoporphyrin Concentrations in Erythrocytes
  • Ferrochelatase Activity Measurement and FECH mRNA Quantification

• Inheritance and Genetic Defects
  • Erythropoietic Protoporphyria
  • X-Linked Dominant Protoporphyria

• Treatment Options
  • Conditioned Behavior and Efficacy Assessment
  • Physical Photoprotection by Clothing
  • Medical Interventions to Prevent Phototoxicity
  • Protoporphyrin-Related Liver Disease

• Summary

• References

The following sections are included:

• List of Abbreviations

• Introduction

• Acute Hepatic Porphyria
  • History of Liver Transplantation in Acute Hepatic Porphyria
  • Indications for Liver Transplantation
  • Conservative Treatment of Severe AIP
  • Timing
  • Results
  • Management Considerations
  • Combined Liver and Kidney Transplantation
  • Domino Transplantation
  • Prelude to Liver Transplantation
  • Perspectives for the Future

• Erythropoietic Protoporphyria
  • History of Liver Transplantation
  • Indications for Liver Transplantation
  • Results
  • Complications
  • Management Considerations
  • Prophylaxis
  • Follow-up
  • Hematopoietic Stem Cell Transplantation
  • Perspectives for the Future

• Summary

• References

The following sections are included:

• List of Abbreviations

• Introduction

• Overview of the Porphyrias
  • Heme Biosynthesis in the Porphyrias
  • Classification
  • Enzyme Alterations and Inheritance
  • Genotype–Phenotype Correlations and Factors Modifying Disease Severity
  • Deficiencies of Heme Pathway Enzymes in Other Conditions

• Diagnostic Considerations in the Porphyrias
  • Porphyrin Precursors and Porphyrins — Properties and Routes of Excretion
  • Three Most Common Porphyrias
  • A Staged Approach to Laboratory Diagnosis of Porphyrias

• Acute Porphyrias
  • Clinical Features and Indications for Testing
  • First-line Testing for Acute Porphyrias
  • Second-line Testing for Acute Porphyrias
  • Additional Testing When Urine PBG is Normal
  • Testing for ADP and Other Causes of ALAD Deficiency
  • Other Laboratory Findings in Acute Porphyrias

• Blistering Cutaneous Porphyrias
  • Clinical Features and Indications for Testing
  • First-line Testing
  • Second-line Testing
  • Other Diagnostic Considerations

• Non-Blistering Photosensitivity — EPP
  • Clinical Features and Indications for Testing
  • First-line Testing
  • Second-line Testing

• Dual Porphyria

• Porphyria Due to Tumors

• Acknowledgments

• References

The following sections are included:

• List of Abbreviations

• Introduction and Current Therapies

• Animal Models

• Enzyme Replacement Therapy

• Liver Gene Therapy
  • Non-viral Delivery Systems
  • Viral Vectors

• Preclinical Studies with rAAV Vectors
  • Development of a Safe and Manufacturing Process of rAAV Vectors for Clinical Studies
  • Preclinical Toxicology Studies
  • Potential Risk Concerns

• Future Directions and Concluding Remarks

• Acknowledgments

• References

The following sections are included:

• List of Abbreviations

• Introduction: Molecular Basis for Erythropoietic Porphyrias

• Animal Models of Erythropoietic Porphyrias
  • Animal Models of Erythropoietic Protoporphyria
  • Animal Models of Congenital Erythropoietic Porphyria
  • Animal Models of Porphyria Cutanea Tarda and Hepatoerythropoietic Porphyria

• Allogeneic Bone Marrow Transplantation for Erythropoietic Porphyrias
  • Allogeneic Bone Marrow Transplantation for Congenital Erythropoietic Porphyria
  • Allogeneic Bone Marrow Transplantation for Erythropoietic Protoporphyria

• Ex Vivo Hematopoietic Stem Cell Gene Therapy
  • Considerations on Cells and Vectors for Hematopoietic Stem Cell Gene Therapy of Erythropoietic Porphyrias
  • Gene Therapy for Hepatoerythropoietic Porphyria
  • Gene Therapy for Congenital Erythropoietic Porphyria
  • Gene Therapy for Erythropoietic Protoporphyria

• Perspectives in Regenerative Medicine for Erythropoietic Porphyrias
  • Progress in Stem Cell Source: Induced Pluripotent Stem Cells
  • Progress in Gene Therapy: Targeted Gene Correction

• Conclusions

• References

The following sections are included:

• Index to Volume 29