Porphyria

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The porphyrias are a "diverse group of metabolic diseases characterized by errors in the biosynthetic pathway of heme in the liver, the bone marrow, or both. They are classified by the deficiency of specific enzymes, the tissue site of enzyme defect, or the clinical features that include neurological (acute) or cutaneous (skin lesions)."^[1][2][3]

Etiology / cause[edit]

Porphyrias are metabolic diseases in the heme biosynthetic pathway characterized by buildup of porphyrin precursors such as porphobilinogen (PBG).

"Porphyrias can be hereditary or acquired as a result of toxicity to the hepatic or erythropoietic marrow tissues."^[1]

Medications may precipitate attacks, especially medications that induce cytochrome P-450.^[3] Cytochrome P-450 is a hemeprotein that consists of a heme group and heme is iron with a porphyrin ring. A database of relevant medications is online.^[4]

Classification[edit]

Diagnosis[edit]

Patients may have pink or red urine from the porphyrins.

Neurovisceral attacks[edit]

The frequency of various signs and symptoms have been tabulated.^[2]

Although the three adult onset neurovisceral porphyrias are autosomal dominant, only 80% of carriers are symptomatic so patients may not report a family history of porphyria.

Laboratory tests[edit]

Rapid urine tests during an acute neurovisceral attack are the Trace and the Hoesch or Watson–Schwartz test for porphobilinogen (PBG).

The best laboratory tests during an acute neurovisceral attack are the 5-aminolevulinic acid (ALA) and PBG in urine or serum.

When considering adult patients with neurovisceral symptoms, all three of the relevant porphyrias (AIP, HCP, VP) have elevated urinary PBG levels (20 to 200 mg/L; 220 to 880 µmol/d).^[2] This level may be elevated to a lesser degree between attacks.

Treatment[edit]

Treatment is administration of hemin and glucose. Precipitating causes should be removed.^[2]

Historical patients[edit]

The insanity exhibited by King George III evidenced in the regency crisis of 1788 has inspired several attempts at retrospective diagnosis. The first, written in 1855, thirty-five years after his death, concluded he suffered from acute mania. M. Guttbacker, in 1941, suggested manic-depressive psychosis as a more likely diagnosis, The first suggestion that a physical illness was the cause of King George's mental derangements came in 1966, in a paper "The Insanity of King George III: A Classic Case of Porphyria"^[5], with a follow-up in 1968, "Porphyria in the Royal Houses of Stuart, Hanover and Prussia"^[6]. The papers, by a mother/son psychiatrist team, were written as though the case for porphyria had been proven, but the response demonstrated that many, including those more intimately familiar with actual manifestations of porphyria, were unconvinced. The theory is treated in Purple Secret^[7], which documents the ultimately unsuccessful search for genetic evidence of porphyria in the remains of royals suspected to suffer from it.^[8] In 2005 it was suggested that arsenic (which is known to be porphyrogenic) given to George III with antimony may have caused his porphyria.^[9] Despite the lack of direct evidence, the notion that George III (and other members of the royal family) suffered from porphyria has achieved such popularity that many forget that it is merely a hypothesis.

It is also suspected that Mary Queen of Scots--George III's grandmother six times removed--also suffered from acute intermittent porphyria, although this is subject to much debate.

Other commentators have suggested that Vincent van Gogh may have suffered from acute intermittent porphyria.^[10]

References[edit]

External links[edit]

• The Drug Database for Acute Porphyria
  • Search database
• Porphyria - A Patient's Guide
• http://www.porphyriafoundation.com/ American Porphyria Foundation