Porphyria

Ravindra Kumar Garg MD (Dr. Garg of King George's Medical University in Lucknow, India, has no relevant financial relationships to disclose.)
Zachary N London MD, editor. (Dr. London of the University of Michigan has no relevant financial relationships to disclose.)
Originally released September 8, 2000; last updated May 12, 2017; expires May 12, 2020

This article includes discussion of porphyria, acute intermittent porphyria, acute porphyria, porphyric encephalopathy, porphyric neuropathy, and Waldenstrom porphyria. The foregoing terms may include synonyms, similar disorders, variations in usage, and abbreviations.

Overview

Porphyrias are a group of metabolic disorders, usually genetic in origin, secondary to deficiencies of various enzymes involved in the heme biosynthesis. Each deficiency is associated with a characteristic increase in heme precursors that allows accurate diagnosis. Porphyrias typically affect nervous system and skin. Potentially life-threatening neurovisceral attacks in patients with porphyria are often precipitated by drugs, fasting, hormonal changes, or infectious diseases. There may be 4 categories of neuropsychiatric manifestations: seizures, polyneuropathy, transient sensory-motor symptoms, and cognitive or behavioral abnormalities. Hyponatremia and hypomagnesemia are common electrolyte abnormalities seen in acute attack. Both the electrolyte changes are risk factors for development of seizures. Acute inherited porphyria should always be considered in patients with acute polyneuropathy or encephalopathy. In several patients, a posterior reversible encephalopathy syndrome and cerebral vasospasm have been described. Porphyric neuropathy resembles acute Guillain-Barré syndrome. Electrodiagnostic findings indicate an axonal neuropathy. Axonal dysfunction is, possibly, linked to the effects of neural energy deficits acquired through haem deficiency along with the neurotoxic effects of porphyrin precursors. Treatment of seizures is particularly problematic as many of the commonly used anticonvulsants are contraindicated in porphyria. Heme therapy can induce a definite remission if given early in an attack. A gonadotropin-releasing hormone analogue can prevent cyclical attacks of porphyria by preventing ovulation. Gene therapy and liver transplantation are exciting future treatment possibilities. In a phase 1, open label, multicenter clinical trial, investigators showed that the administration of porphobilinogen deaminase gene rAAV2/5-PBGD to patients with severe acute intermittent porphyria is safe but not effective. In this article, the author discusses the history, clinical features, pathophysiology, classification, and treatment of porphyria.

Key points

 

• Porphyrias are a group of genetic disorders caused by mutations in enzymes of the heme biosynthesis pathway.

 

• Porphyrias present acutely in attacks, consisting of severe abdominal pain, nausea, constipation, confusion, and seizure, and can be life-threatening.

 

• The precipitating factors include drugs, steroid hormones, anesthetic agents, severe fasting, stress, infections, smoking, and alcohol.

 

• Porphyric neuropathy is manifest by symptoms, signs, and cerebrospinal fluid abnormalities resembling acute Guillain-Barré syndrome.

 

• A high index of suspicion is required to make the diagnosis.

 

• Heme therapy is effective when given early in the course of an attack.

 

• Gene therapy and liver transplantation are exciting future treatment possibilities.

Historical note and terminology

The word “porphyria” derives from the Greek word “porphyrus,” which means red or purple. Stokvis reported the first case of porphyria in 1889, and Campbell described its pathology in 1898 (Stokvis 1889; Campbell 1898). Early in the twentieth century, Waldenstrom called this disease a little imitator in distinction to the more common manifestations of neurosyphilis. Clinical observations by Waldenstrom (Sweden) and Watson (United States) served to better define the condition (Waldenstrom 1937; Waldenstrom 1957; Watson 1954). In 1969, it was proposed that the episodic madness suffered by King George III (1738 to 1820) resulted from an acute hereditary porphyria, variegate porphyria. Even episodic psychiatric illness of Vincent van Gogh was considered to be because of porphyria. Archibald Cochrane, one of the founders of evidence-based medicine, also suffered from porphyria. Various studies have greatly advanced the molecular genetic basis of the disease (Kappas et al 1995; Voskuil 2005).

The content you are trying to view is available only to logged in, current MedLink Neurology subscribers.

If you are a subscriber, please log in.

If you are a former subscriber or have registered before, please log in first and then click select a Service Plan or contact Subscriber Services. Site license users, click the Site License Acces link on the Homepage at an authorized computer.

If you have never registered before, click Learn More about MedLink Neurology  or view available Service Plans.