Differential Diagnoses

Workup

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Media Gallery

Heme production pathway. Heme production begins in the mitochondria, proceeds into the cytoplasm, and resumes in the mitochondria for the final steps. Figure outlines the enzymes and intermediates involved in the porphyrias. Names of enzymes are presented in the boxes; names of the intermediates, outside the boxes. Multiple arrows leading to a box demonstrate that multiple intermediates are required as substrates for the enzyme to produce 1 product.

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Table 1. Known Chromosomal Location of Enzymes Involved in Porphyria and Inheritance Patterns

Type of Porphyria	Deficient Enzyme	Location	Inheritance Pattern	Band
ALAD deficiency	ALAD	Cytosol	Autosomal recessive	9q34
AIP	PBG deaminase	Cytosol	Autosomal dominant	11q23
HCP	Coproporphyrinogen oxidase	Mitochondrial	Autosomal dominant	3q12
VP	Protoporphyrinogen oxidase	Mitochondrial	Autosomal dominant	1q22-23

Table 2. Frequencies of Porphyria

Type of Porphyria	Age of Onset	Incidence	Male-to-Female Ratio
ALAD deficiency	Mostly adolescence to young adulthood, but variable (2-63 y)	6 cases total	6:0
AIP	After puberty (third decade)	General 0.01/1000 Sweden 1/1000 Finland 2/1000 France 0.3/1000	M>F
HCP	Predominantly adulthood (youngest patient aged 4 y)	Japan 0.015/1000 Czech 0.015/1000 Israel 0.007/1000 Denmark 0.0005/1000	1:20 1:4 2:1 1:1
VP	Heterozygous mutation: after puberty (fourth decade) Homozygous mutation (rare): childhood	South Africa 0.34/1000	1:1

Table 3. Quantitative Urine Porphyrin Levels

Level	ALAD Deficiency	Acute Intermittent Porphyria (AIP)	Congenital Erythropoietic Porphyria (CEP) and Porphyria Cutanea Tarda (PCT)	HCP and VP
ALA	Significantly increased	Significantly increased	Normal	Significantly increased
PBG	Increased	Significantly increased	Normal	Significantly increased
Uroporphyrin	Normal	Increased	Significantly increased	Increased
Coproporphyrin	Significantly increased	Increased	Increased	Significantly increased

Table 4. Quantitative Stool Porphyrin levels

Level	HCP	VP
Coproporphyrin	Significantly increased	Increased
Protoporphyrin	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)

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

Lawrence C Wolfe, MD Associate Chief for Hematology and Safety, Division of Pediatric Hematology-Oncology, Cohen Children's Medical Center

Lawrence C Wolfe, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Pediatrics, American Association of Blood Banks, American Society of Hematology, Children's Oncology Group, Eastern Society for Pediatric Research

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.