The acute porphyrias, 4 inherited disorders of heme biosynthesis, cause life-threatening attacks of neurovisceral symptoms that mimic many other acute medical and psychiatric conditions. Lack of clinical recognition often delays effective treatment, and inappropriate diagnostic tests may lead to misdiagnosis and inappropriate treatment. We review the clinical manifestations, pathophysiology, and genetics of the acute porphyrias and provide recommendations for diagnosis and treatment on the basis of reviews of the literature and clinical experience.
An acute porphyria should be considered in many patients with unexplained abdominal pain or other characteristic symptoms. The diagnosis can be rapidly confirmed by demonstration of a markedly increased urinary porphobilinogen level by using a single-void urine specimen. This specimen should also be saved for quantitative measurement of porphobilinogen, 5-aminolevulinic acid, and total porphyrin levels. Intravenous hemin therapy, started as soon as possible, is the most effective treatment. Intravenous glucose alone is appropriate only for mild attacks (mild pain, no paresis or hyponatremia) or until hemin is available. Precipitating factors should be eliminated, and appropriate supportive and symptomatic therapy should be initiated. Prompt diagnosis and treatment greatly improve prognosis and may prevent development of severe or chronic neuropathic symptoms. We recommend identification of at-risk relatives through enzymatic or gene studies.
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Author, Article, and Disclosure Information
From the University of Texas Medical Branch, Galveston, Texas; University of Alabama at Birmingham, Birmingham, Alabama; University of Connecticut Health Center, Farmington, Connecticut; University of Utah School of Medicine, Salt Lake City, Utah; University of Minnesota School of Medicine, Minneapolis, Minnesota; University of California Davis Medical Center, Sacramento, California; Mount Sinai School of Medicine of New York University, New York, New York.
Acknowledgments: The authors thank Desiree Lyon Howe, Executive Director of the American Porphyria Foundation, for her support of the manuscript, and Lisa Underhill for writing assistance.
Grant Support: This review was supported in part by the American Porphyria Foundation, by grants to Dr. Anderson from the U.S. Food and Drug Administration (FD-R-00-1459) and a grant to the University of Texas Medical Branch General Clinical Research Center from the National Center for Research Resources (M01-RR0073); by grants and contracts to Dr. Bonkovsky from the National Institutes of Health (including R01 DK38825, N01DK92326, and U01-DK065193, and M01-RR06192 to the University of Connecticut General Clinical Research Center); and by grants to Dr. Desnick from the National Institutes of Health (including a research grant (5 R01 DK26824) and a grant (2 M01 RR00071) to the Mount Sinai General Clinical Research Center from the National Center for Research Resources).
Disclosures: Grants pending: K.E. Anderson (Ovation Pharmaceuticals); Grants received: J.R. Bloomer (Ovation Pharmaceuticals).
Corresponding Author: Robert J. Desnick, PhD, MD, Department of Human Genetics, Mount Sinai School of Medicine, Box 1498, Fifth Avenue at 100th Street, New York, NY 10029; e-mail, [email protected]
Current Author Addresses: Dr. Anderson: Departments of Preventative Medicine and Community Health, Internal Medicine, and Pharmacology and Toxicology, University of Texas Medical Branch, 700 Harborside Drive, Galveston, TX 77555.
Dr. Bloomer: Departments of Medicine and Genetics, University of Alabama at Birmingham, 395 BHSH, 1918 University Boulevard, Birmingham, AL 35294.
Dr. Bonkovsky: Departments of Medicine and Molecular, Microbial, and Structural Biology, University of Connecticut Health Center, 263 Farmington Avenue, Farmington, CT 06030.
Dr. Kushner: Department of Medicine, University of Utah School of Medicine, 30 North 1900 East Room, 4C416, Salt Lake City, UT 84132.
Dr. Pierach: Department of Medicine, Abbott Northwestern Hospital, University of Minnesota School of Medicine, 800 East 28th Street, Minneapolis, MN 55407.
Dr. Pimstone: Department of Internal Medicine, University of California Davis Medical Center, 4150 V Street, Suite 3500, Sacramento, CA 95817.
Dr. Desnick: Department of Human Genetics, Mount Sinai School of Medicine, Box 1498, Fifth Avenue at 100th Street, New York, NY 10029.
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