Porphyria

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). Porphyrias can be hereditary or acquired as a result of toxicity to the hepatic or erythropoietic marrow tissues."

Classification

Classification of porphyrias

Name	Onset	Other
Cutaneous involvement
Congenital erythropoietic porphyria	Infancy
Erythropoietic protoporphyria	Infancy
Hepatoerythropoietic porphyria	Infancy
Porphyria cutanea tarda	Adulthood	Most common porphyria. May be acquired
Neurovisceral involvement
ALA-dehydratase deficient porphyria (ADP) OMIM 125270	Childhood
Acute intermittent porphyria (AIP) OMIM 176000	Adulthood	Most common neurovisceral porphyria.
Hereditary coproporphyria (HCP) OMIM 121300	Adulthood	Sometimes has cutaneous involvement.
Variegate porphyria (VP) OMIM 176200	Adulthood	Sometimes has cutaneous involvement.

Diagnosis

Patients may have pink or red urine from the porphyrins.

Neurovisceral attacks

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.

The best laboratory tests during an acute neurovisceral attack are the 5-aminolevulinic acid (ALA) and porphobilinogen in urine or serum. An alternative, rapid test is the urine Hoesch or Watson–Schwartz test for porphobilinogen.

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

Historical patients

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", with a follow-up in 1968, "Porphyria in the Royal Houses of Stuart, Hanover and Prussia". 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, which documents the ultimately unsuccessful search for genetic evidence of porphyria in the remains of royals suspected to suffer from it. In 2005 it was suggested that arsenic (which is known to be porphyrogenic) given to George III with antimony may have caused his porphyria. 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.