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Media Gallery

The heme production pathway. Heme production begins in the mitochondria, proceeds into the cytoplasm, and is then resumed in the mitochondria for the final steps. This figure outlines the enzymes and intermediates involved in the porphyrias. Enzymes names are presented in the boxes. Names of the intermediates are outside the boxes, between arrows. Multiple arrows leading to a box demonstrate that multiple intermediates are required as substrates for the enzyme to produce one product.

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Table 1. Frequency Varies with the Specific Porphyria

Type of Porphyria	Age of Onset	Incidence per 100,000 Population	Male-to-Female Ratio
CEP	Infancy to early childhood; rare in adults	300 cases total	1:1
PCT	Type I: Adulthood Type II (heterozygous mutations): Adulthood Type III (homozygous mutations): Childhood	United States: 4 United Kingdom: 0.05	1:1
HCP	Predominantly adulthood Youngest report was child aged 4 y	Japan: 1.5 Czech: 1.5 Israel: 0.7 Denmark: 0.05	1:20 1:4 2:1 1:1
VP	Heterozygous mutation: After puberty Homozygous mutation: Childhood (rare)	South Africa: 34	1:1
EPP	Infancy to childhood	0.02	1:1

Table 2. Causes by Type of Porphyria

Porphyria	Deficient Enzyme	Location	Inheritance	Chromosome Band
CEP	Uroporphyrinogen III synthase	Cytosol	Autosomal recessive (AR)	10q25.3-26.3
PCT	Uroporphyrinogen decarboxylase	Cytosol	Autosomal dominant (AD)	1p34
HEP	Uroporphyrinogen decarboxylase	Cytosol	AR	1p34
HCP	Coproporphyrinogen oxidase	Mitochondrial	AD	3q12
VP	Protoporphyrinogen oxidase	Mitochondrial	AD	1q22-23
EPP	Ferrochelatase	Mitochondrial	AD, AR	18q22

Table 3. Quantitative Fecal Porphyrins by Type of Porphyria

Porphyrin Type	CEP	PCT	HCP	VP	EPP
Uroporphyrin	Significantly increased	Increased	Within reference range	Within reference range	Within reference range
Coproporphyrin	Significantly increased	Increased	Significantly increased	Increased	Within reference range
Protoporphyrin	Within reference range	Within reference range	Increased	Significantly increased	Significantly increased

Table 4. Quantitative Urine Porphyrins

Porphyrin type	CEP and PCT	HCP and VP
5-Aminolevulinate	Within reference range	Significantly increased
PBG	Within reference range	Significantly increased
Uroporphyrin	Significantly increased	Increased
Coproporphyrin	Increased	Significantly increased

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Author

Richard E Frye, MD, PhD Professor of Child Health, University of Arizona College of Medicine at Phoenix; Chief of Neurodevelopmental Disorders, Director of Autism and Down Syndrome and Fragile X Programs, Division of Neurodevelopmental Disorders, Department of Neurology, Barrow Neurological Institute at Phoenix Children's Hospital

Richard E Frye, MD, PhD is a member of the following medical societies: American Academy of Neurology, American Academy of Pediatrics, Child Neurology Society

Disclosure: Nothing to disclose.

Coauthor(s)

Darius J Adams, MD Director, Personalized Genomic Medicine, Atlantic Health System; Director, Division of Genetics and Metabolism, Goryeb Children's Hospital

Disclosure: Nothing to disclose.

Thomas G DeLoughery, MD Professor of Medicine, Pathology, and Pediatrics, Divisions of Hematology/Oncology and Laboratory Medicine, Associate Director, Department of Transfusion Medicine, Division of Clinical Pathology, Oregon Health and Science University School of Medicine

Thomas G DeLoughery, MD is a member of the following medical societies: American Association for the Advancement of Science, American Association of Blood Banks, American College of Physicians, American Society of Hematology, International Society on Thrombosis and Haemostasis, Wilderness Medical Society

Disclosure: Nothing to disclose.

Specialty Editor Board

Mary L Windle, PharmD Adjunct Associate Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Nothing to disclose.

James L Harper, MD Associate Professor, Department of Pediatrics, Division of Hematology/Oncology and Bone Marrow Transplantation, Associate Chairman for Education, Department of Pediatrics, University of Nebraska Medical Center; Associate Clinical Professor, Department of Pediatrics, Creighton University School of Medicine; Director, Continuing Medical Education, Children's Memorial Hospital; Pediatric Director, Nebraska Regional Hemophilia Treatment Center

James L Harper, MD is a member of the following medical societies: American Society of Pediatric Hematology/Oncology, American Federation for Clinical Research, Council on Medical Student Education in Pediatrics, Hemophilia and Thrombosis Research Society, American Academy of Pediatrics, American Association for Cancer Research, American Society of Hematology

Disclosure: Nothing to disclose.

Chief Editor

Hassan M Yaish, MD Medical Director, Intermountain Hemophilia and Thrombophilia Treatment Center; Professor of Pediatrics, University of Utah School of Medicine; Director of Hematology, Pediatric Hematologist/Oncologist, Department of Pediatrics, Primary Children's Medical Center

Hassan M Yaish, MD is a member of the following medical societies: American Academy of Pediatrics, American Medical Association, American Society of Hematology, American Society of Pediatric Hematology/Oncology, Michigan State Medical Society, New York Academy of Sciences

Disclosure: Nothing to disclose.

Additional Contributors

Sharada A Sarnaik, MBBS Professor of Pediatrics, Wayne State University School of Medicine; Director, Sickle Cell Center, Associate Hematologist/Oncologist, Children's Hospital of Michigan

Sharada A Sarnaik, MBBS is a member of the following medical societies: American Society of Hematology, American Society of Pediatric Hematology/Oncology, New York Academy of Sciences, Society for Pediatric Research, Children's Oncology Group, American Academy of Pediatrics, Midwest Society for Pediatric Research

Disclosure: Nothing to disclose.

Acknowledgements

Vikramjit S Kanwar, MD, MBA, MRCP(UK), FAAP Associate Professor of Pediatric Hematology and Oncology, Department of Pediatrics, Albany Medical Center; Faculty, Alden March Bioethics Institute

Vikramjit S Kanwar, MD, MBA, MRCP(UK), FAAP is a member of the following medical societies: American Academy of Pediatrics, American Society of Pediatric Hematology/Oncology, Children's Oncology Group, and Royal College of Physicians of the United Kingdom

Disclosure: Nothing to disclose.