A group of inherited disorders involving the excess production of chemical substances known as porphyrins. They cause a wide range of abnormalities, including sensitivity of the skin to sunlight, pigmentation of the skin, abdominal pain, and mental confusion. It entered the British royal family through Mary, Queen of Scots, and symptoms were displayed by the Stuarts. It then passed to the Hanoverians, and was most acutely displayed in the supposed madness of George III. It is sometimes called the royal malady, not because of its royal connections, but due to the production of purple urine.
PorphyriaClassifications and external resources
| ICD-10 | E80.0-E80.2 | |
|---|---|---|
| ICD-9 | 277.1 | |
| MedlinePlus | 001208 | |
| MeSH | C17.800.849.617 | |
The porphyrias are inherited or acquired disorders of certain enzymes in the heme biosynthetic pathway (also called porphyrin pathway). Although original descriptions are attributed to Hippocrates, the disease was first explained biochemically by Felix Hoppe-Seyler in 1874, and acute porphyrias were described by the Dutch physician B.J.
Signs and symptoms
Acute porphyria
The hepatic porphyrias primarily affect the nervous system, resulting in abdominal pain, vomiting, acute neuropathy, seizures, and mental disturbances, including hallucinations, depression, anxiety, and paranoia.
Given the many presentations and the relatively uncommon occurence of porphyria the patient may initially be suspected to have other, unrelated conditions. For instance, the polyneuropathy of acute porphyria may be mistaken for Guillain-Barré syndrome, and porphyria testing is commonly recommended in those scenarios. Lupus erythematosus features photosensitivity, pain attacks and shares various other symptoms with porphyria.
Not all porphyrias are genetic, and patients with liver disease who develop porphyria as a result of liver dysfunction may exhibit signs of their conditions, such as jaundice.
Patients with hepatic porphyrias (PCT, AIP, HCP, VP) are at increased risk over their life for hepatocellular carcinoma (primary liver cancer) and may require monitoring.
Cutaneous porphyria
The erythropoietic porphyrias primarily affect the skin, causing photosensitivity (photodermatitis), blisters, necrosis of the skin and gums, itching, and swelling, and increased hair growth on areas such as the forehead.
In some forms of porphyria, accumulated heme precursors excreted in the urine may change its color, after exposure to sunlight, to a dark reddish or dark brown color.
Diagnosis
Porphyrin studies
Porphyria is diagnosed through spectroscopy and biochemical analysis of blood, urine, and stool. In general, urine estimation of porphobilinogen (PBG) is the first step if acute porphyria is suspected. In nearly all cases of acute porphyria syndromes, urinary PBG is markedly elevated except for the very rare ALA dehydratase deficiency or in patients with symptoms due to lead poisoning or hereditary tyrosinemia type I.
Repeat testing during an attack and subsequent attacks may be necessary in order to detect a porphyria, as levels may be normal or near-normal between attacks. The urine screening test has been known to fail in the initial stages of a severe life threatening attack of acute intermittent porphyria.
The bulk (up to 90%) of the genetic carriers of the more common, dominantly inherited acute hepatic porphyrias (acute intermittent porphyria, hereditary coproporphyria, variegate porphyria) have been noted in DNA tests to be latent for classic symptoms and may require DNA or enzyme testing.
As most porphyrias are rare conditions, general hospital labs typically do not have the expertise, technology or staff time to perform porphyria testing.
The hepatic porphyrias are characterized by acute neurological attacks (seizures, psychosis, extreme back and abdominal pain and an acute polyneuropathy), while the erythropoietic forms present with skin problems, usually a light-sensitive blistering rash and increased hair growth.
Variegate porphyria (also porphyria variegata or mixed porphyria), which results from a partial deficiency in PROTO oxidase, manifests itself with skin lesions similar to those of porphyria cutanea tarda combined with acute neurologic attacks.
| Enzyme | Location of enzyme | Associated porphyria | Type of porphyria |
| δ-aminolevulinate (ALA) synthase | Mitochondrium | X-linked sideroblastic anemia (XLSA) | Erythropoietic |
| δ-aminolevulinate (ALA) dehydratase | Cytosol | Doss porphyria/ALA dehydratase deficiency | Hepatic |
| hydroxymethylbilane (HMB) synthase (or PBG deaminase) | Cytosol | acute intermittent porphyria (AIP) | Hepatic |
| uroporphyrinogen (URO) synthase | Cytosol | Congenital erythropoietic porphyria (CEP) | Erythropoeitic |
| uroporphyrinogen (URO) decarboxylase | Cytosol | Porphyria cutanea tarda (PCT) | Hepatic |
| coproporphyrinogen (COPRO) oxidase | Mitochondrium | Hereditary coproporphyria (HCP) | Hepatic |
| protoporphyrinogen (PROTO) oxidase | Mitochondrium | Variegate porphyria (VP) | Mixed |
| Ferrochelatase | Mitochondrium | Erythropoietic protoporphyria (EPP) | Erythropoietic |
Treatment
Acute porphyria
Carbohydrates and hemeOften, empirical treatment is required if the diagnostic suspicion of a porphyria is high since acute attacks can be fatal.
Hematin and haem arginate are the drugs of choice in acute porphyria, in the United States and the United Kingdom, respectively.
Early identificationPatients with a history of acute porphyria and even genetic carriers are recommended to wear an alert bracelet or other identification at all times in case they develop severe symptoms or in case of accidents where there is a potential for drug exposure: a result of which may be they cannot explain to healthcare professionals about their condition and the fact that some drugs are absolutely contraindicated.
Magnesium sulfate and bromides have also been used in porphyria seizures, however, development of status epilepticus in porphyria may not respond to magnesium alone.
Underlying liver diseaseSome liver diseases may cause porphyria even in the absence of genetic predisposition.
Erythropoietic porphyrias
The skin rash that occurs in erythropoietic porphyrias generally requires use of sunscreen and avoidance of bright sunlight.
Culture and history
Vampires and werewolves
Porphyria has been suggested as an explanation for the origin of vampire and werewolf legends, based upon a number of similarities between the condition and the folklore that was first speculated upon by biochemist David Dolphin in 1985. Porphyria cutanea tarda presents clinically as a pathological sensitivity of skin exposed to light causing scarring, hair growth and disfiguration.
Porphyrias have been detected in all races, multiple ethnic groups on every continent including Caucasians, Asians, Africans, Peruvian/Mexican Hispanics, Native Americans, Laplanders and Australian aborigines.
The Scandinavian source of porphyria has been traced to the Sámi ethnic group.
The links between porphyrias and mental illness have been noted for decades. In the early 1950's patients with porphyrias (occasionally referred to as "Porphyric Hemophilia") and severe symptoms of depression or catatonia were treated with electroshock. 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. Despite the lack of 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.
Other commentators have suggested that Vincent van Gogh may have suffered from acute intermittent porphyria.
It has also been imagined that King Nebuchadnezzar of Babylon suffered from some form of porphyria (cf. The symptoms of the various porphyrias are so wide-ranging that nearly any constellation of symptoms can be attributed to one or more of them.
User Comments Add a comment…