Acute Porphyria Treatment & Management

Author: Richard E Frye, MD, PhD; Chief Editor: Max J Coppes, MD, PhD, MBA more...

Updated: Mar 12, 2012

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Medical Care
Consultations
Diet
Activity
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Medical Care

Consider an appropriate period of first-line conservative therapy in patients with acute porphyria before administering heme for injection. The duration of conservative treatment depends on the patient's presenting condition and clinical course. Start a hematin infusion immediately if clinical deterioration is evident to prevent neuronal damage.

Conservative first-line therapy includes the following:

Remove potentially offending medications.
Administer intravenous (IV) fluid with a substantial carbohydrate supply (eg, dextrose 500 g/d).
Control pain with opiates.
Relieve nausea and vomiting with phenothiazines.

If conservative treatment proves unsatisfactory, administer an IV heme infusion for 3-14 days.

Hematin is the only heme compound currently approved for use in the United States. Heme arginate (Normosang) is a more stable heme compound and has a lower frequency of adverse effects. Although this compound has been used with success in Europe and South Africa, it has not been approved for use in the United States.

Heme requires prompt administration for clinical benefit. Episodes of porphyria can cause irreversible neuronal damage. Heme therapy is intended to prevent an episode from reaching the critical stage of neuronal degeneration.

Fecal urobilinogen increases in proportion to the amount of hematin administered; this observation suggests an enterohepatic pathway as a route of elimination. Bilirubin metabolites are also excreted in the urine after hematin administration.

Urinary concentrations of porphyrins can be followed to monitor treatment efficacy. A decrease in aminolevulinic acid (ALA), uroporphyrinogen, porphobilinogen (PBG), and/or coproporphyrin values indicates successful treatment.

Strictly follow recommended dosing guidelines because asymptomatic reversible renal shutdown can occur when a greatly excessive dose of hematin is administered in a single infusion. However, recommended doses of hematin do not impair renal function.

Liver transplantation was effective in a case of severe acute intermittent porphyria (AIP). Studies of gene therapy in animal models to restore PBG activity are ongoing.

Several factors complicate the treatment of seizures in porphyria. The liver metabolizes most anticonvulsants are metabolized, at least to some extent, and most anticonvulsants induce the cytochrome P-450 enzyme system.

Acute seizure control includes the following:

Magnesium sulfate and diazepam are first-line drugs for acute seizure control.
Lorazepam is generally the first-line drug for status epilepticus and is safe to use in patients with porphyria.
Correct acute electrolyte abnormalities because seizures are commonly associated with such abnormalities.

Epilepsy control includes the following:

Gabapentin is not metabolized by the liver and is reportedly successful for long-term seizure control.
Diazepam per rectal is useful for outpatient control of prolonged seizures.

Correct electrolyte abnormalities. Hyponatremia can be corrected with an infusion of normal saline or half normal saline, depending on the level of volume depletion and hyponatremia. However, fluid restriction and diuretics may be needed if the patient exhibits signs of syndrome of inappropriate antidiuretic hormone secretion.

Autonomic outflow is managed by the administration of beta-blockers. Acute hypertension must be managed with appropriate emergency agents.

Psychiatric symptoms are typically controlled by administering phenothiazines (eg, chlorpromazine). These medications can also help relieve nausea.

Consultations

An expert in porphyria should assist in the diagnosis and treatment of patients with acute and chronic cases, as the management of porphyria involves many disciplines. Such experts may be certified in metabolic diseases, gastroenterology, or hematology.

Consultation with a neurologist may be needed if seizures or neuropathy develop.

Consultation with a physical therapist may be needed if muscle weakness develops.

Consultation with a psychiatrist may be necessary for the management of short-term and/or long-term psychiatric issues.

Consultation with a specialist in reproductive medicine may be necessary for menses and birth control.

Consultation with a cardiologist may be needed if hypertension develops.

Consultation with an anesthesiologist is necessary before a patient is sedated for a minor procedure or surgery.

Seek a consultation with an ophthalmologist if ocular manifestations arise.

Diet

A high-carbohydrate diet can mitigate the disease. A low-carbohydrate diet is strictly forbidden.

The patient should maintain adequate fluid intake to ensure good clearance of porphyrins.

A low-salt, low-fat, and low-cholesterol diet may be prudent if hypertension develops.

Activity

Instruct patients to avoid activities that put them at risk for dehydration, exhaustion, or carbohydrate depletion.

Proceed to Medication

Contributor Information and Disclosures

Author

Richard E Frye, MD, PhD Assistant Professor, Departments of Pediatrics and Neurology, University of Texas Medical School at Houston

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

Disclosure: Nothing to disclose.

Specialty Editor Board

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

Sharada A Sarnaik, MBBS is a member of the following medical societies: American Association of Blood Banks, American Association of University Professors, American Society of Hematology, American Society of Pediatric Hematology/Oncology, New York Academy of Sciences, and Society for Pediatric Research

Disclosure: Nothing to disclose.

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; Assistant 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 Academy of Pediatrics, American Association for Cancer Research, American Federation for Clinical Research, American Society of Hematology, American Society of Pediatric Hematology/Oncology, Council on Medical Student Education in Pediatrics, and Hemophilia and Thrombosis Research Society

Disclosure: Nothing to disclose.

Helen SI Chan, MBBS, FRCP(C), FAAP Associate Senior Scientist, Research Institute; Professor, Division of Hematology/Oncology, Department of Pediatrics, The Hospital for Sick Children, University of Toronto Faculty of Medicine, Canada

Helen SI Chan, MBBS, FRCP(C), FAAP is a member of the following medical societies: American Academy of Pediatrics, American Association for Cancer Research, American Society of Hematology, and Royal College of Physicians and Surgeons of Canada

Disclosure: Nothing to disclose.

Chief Editor

Max J Coppes, MD, PhD, MBA Senior Vice President, Center for Cancer and Blood Disorders, Children's National Medical Center; Professor of Medicine, Oncology, and Pediatrics, Georgetown University School of Medicine; Clinical Professor of Pediatrics, George Washington University School of Medicine and Health Sciences

Max J Coppes, MD, PhD, MBA is a member of the following medical societies: American Association for Cancer Research, American Society of Pediatric Hematology/Oncology, and Society for Pediatric Research

Disclosure: Nothing to disclose.

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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.

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

View Table List

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