Management and prognosis of acute intermittent porphyria
- Gagan K Sood, MD
Gagan K Sood, MD
- Associate Professor, Department of Surgery and Medicine
- Baylor College of Medicine
- Karl E Anderson, MD, FACP
Karl E Anderson, MD, FACP
- The University of Texas Medical Branch
- Section Editors
- Donald H Mahoney, Jr, MD
Donald H Mahoney, Jr, MD
- Section Editor — Pediatric Hematology
- Professor of Pediatrics
- Baylor College of Medicine
- Stanley L Schrier, MD
Stanley L Schrier, MD
- Editor-in-Chief — Hematology
- Section Editor — Myeloproliferative Disorders; Red Cell Disorders
- Professor of Medicine
- Stanford University School of Medicine
Acute intermittent porphyria (AIP, Swedish porphyria, pyrroloporphyria, intermittent acute porphyria) is an autosomal dominant disorder of low penetrance resulting from a partial deficiency of porphobilinogen deaminase (PBGD, hydroxymethylbilane synthase [HMBS], previously called uroporphyrinogen I synthase), the third enzyme in the heme biosynthetic pathway (figure 1 and figure 2). Symptoms in AIP are due to effects on the visceral, peripheral, autonomic, and central nervous systems. They usually occur as intermittent attacks that are sometimes life-threatening due to neurologic complications (eg, seizures, paralysis).
The management of patients with attacks of AIP can be challenging because the disease manifestations are diverse and potentially life-threatening. Timely intervention can resolve and prevent attacks, and close long-term monitoring for complications is needed. Further, it is important not only to treat the porphyria, but also to address any other condition (eg, infection, medication exposure) that may have triggered the acute attack.
The management of AIP is reviewed here, including treatment of acute attacks, prevention, and long-term monitoring for complications. The clinical manifestations and diagnosis of AIP and a general overview of the porphyrias are presented separately. (See "Pathogenesis, clinical manifestations, and diagnosis of acute intermittent porphyria" and "Porphyrias: An overview".)
TESTING BEFORE THERAPY
Demonstration of an elevation of urinary porphobilinogen (PBG) remains central to the diagnosis of acute porphyria. This finding is specific for the three most common acute porphyrias. Substantial PBG elevation (which occurs only in AIP, hereditary coproporphyria [HCP], and variegate porphyria [VP]) should be established, or have been established in the past, before treatment is started, particularly with hemin. However, therapy for an acute attack does not require differentiation among these types of porphyria. The diagnosis of an attack in a patient with known acute porphyria is primarily clinical.
For patients who require further diagnostic testing to determine the type of porphyria, samples should be obtained prior to initiating therapy if possible, but determination of the specific type of porphyria should not delay therapy. A prior diagnosis of AIP or other acute porphyria cannot be assumed to be correct. Therefore, the evidence for the prior diagnosis should be available for review. If this is not available, a spot urine should be obtained and tested for PBG as soon as possible. Once it is known that an acute porphyria is indeed present, individual attacks are diagnosed and treated based on clinical findings (eg, typical symptoms), although confirmation of PBG elevation with each attack is recommended.
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- TESTING BEFORE THERAPY
- Confirm acute porphyria
- Establish presence of an acute attack
- THERAPY FOR AN ACUTE ATTACK
- Overview of therapy
- Paresis and paralysis
- Treatment of other symptoms
- Intravenous hemin
- Carbohydrate loading
- Elimination of exacerbating factors
- Other treatments
- THERAPY FOR SUBACUTE OR CHRONIC SYMPTOMS
- PREVENTION OF ATTACKS
- MONITORING FOR COMPLICATIONS OF DISEASE AND THERAPY
- LIVER TRANSPLANTATION
- GENETIC COUNSELING
- SUMMARY AND RECOMMENDATIONS