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  • Updated 03.18.2021
  • Released 09.08.2000
  • Expires For CME 03.18.2024

Porphyria

Introduction

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. Many psychiatric manifestations are also seen in patients with acute porphyria. 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. Givosiran is a new investigational drug that has shown promising results in alleviating recurrent attacks of acute intermittent porphyria. A placebo-controlled, randomized trial has demonstrated that the patients with acute intermittent porphyria who received givosiran have a fewer number of porphyria attacks. 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 (64; 16). 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 (73; 74; 76). 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 (33; 72).

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