Karl E. Anderson MD, Professor, Departments of Preventive Medicine and Community Health, Internal Medicine, Pharmacology and Toxicology; Associate Director, General Clinical Research Center, Director, Porphyria Center and Laboratory, University of Texas Medical Branch, Galveston, Texas
Bradley Freilich, MD, Kansas City Gastroenterology and Hepatology, LLC
2. Acute porphyrias cause acute attacks of neurological symptoms that can be life-threatening.
3. Acute attacks are triggered by certain drugs, sex steroid hormones, reduced intake of calories and carbohydrate, alcohol and unknown factors.
4. Many of these factors stimulate heme synthesis in the liver, which in the face of a metabolic enzyme defect, leads to increased production of heme precursors that may be neurotoxic.
5. Delta-aminolevulinic acid (ALA) and porphobilinogen (PBG), are porphyrin precursors and intermediates in the heme biosynthetic pathway.
6. ALA and porphobilinogen (PBG) are almost always elevated in urine during an acute attack of porphyria.
7. The most common emergency room (ER) clinical presentation is acute abdominal pain. Other features may include seizures, confusion and hallucinations, and a progressive polyaxonal motor neuropathy, which can progress to paralysis and respiratory failure requiring a ventilator.
8. A high index of suspicion in the presence of nonspecific symptoms is important for diagnosis. A family history of porphyria, female sex, onset during the luteal phase of the menstrual cycle, or recent use of a porphyrinogenic drug may be diagnostic clues.
9. A new diagnosis of porphyria as the cause of acute symptoms must be substantiated by finding a substantial increase in urine porphobilinogen (PBG).
10. Treatment should start promptly after the diagnosis is made. Mild attacks are sometimes treated with glucose loading (e.g. 3L of 10% glucose daily by vein).
11. Most acute attacks should be treated with hemin (Panhematin®, Recordati Rare Diseases at: www.recordatirarediseases.com or 866-654-0539) 3-4mg/kg into a large peripheral vein or venous access port daily for 4 days. Reconstituting Panhematin® with human serum albumin rather than sterile water is recommended prior to infusion. This helps prevent phlebitis at the site of intravenous infusion.
12. Hospitalization is usually required for symptomatic treatment of pain, nausea and vomiting, correction of electrolyte imbalance and observation for respiratory impairment, either to a general medical service or ICU.