acute intermittent porphyria


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porphyria

 [por-fēr´e-ah]
a genetic disorder characterized by a disturbance in porphyrin metabolism with resultant increase in the formation and excretion of porphyrins (uroporphyrin and coproporphyrin) or their precursors; called also hematoporphyria. Porphyrins, in combination with iron, form hemes, which in turn combine with specific proteins to form hemoproteins. hemoglobin is a hemoprotein, as are many other substances essential to normal functioning of the cells and tissues of the body.

Two general types are known: the erythropoietic porphyrias, which are concerned with the formation of erythrocytes in the bone marrow; and the hepatic porphyrias, which are responsible for liver dysfunction. Manifestations of porphyria include gastrointestinal, neurologic, and psychologic symptoms, cutaneous photosensitivity, pigmentation of the face (and later of the bones), and anemia with enlargement of the spleen. Large amounts of porphyrins are excreted in the urine and feces.

Treatment of this condition has been primarily symptomatic and varies in its effectiveness. Emphasis is on prevention of attacks by avoiding fasting and drugs that precipitate the symptoms. Photosensitivity may be controlled by avoiding exposure to light. Removal of the spleen is useful in some cases of the erythropoietic type of porphyria. Drug therapy includes the use of phenothiazines, chlorpromazine and promazine in particular. These drugs allay pain and nervousness and apparently allow a period of remission from symptoms. Meperidine hydrochloride (Demerol) may be given for pain and hydroxypheme (Hemetin) is given intravenously to compensate for genetic impairment of heme synthesis.

Patients with porphyria must not be given barbiturates, sulfonamides, alcohol, or chloroquine as these chemicals may precipitate or intensify attacks. It is recommended that persons with this disease carry with them at all times identification saying that they have porphyria so that in an emergency they will not be given medication that could precipitate an attack or even death.
acute intermittent porphyria (AIP) a hereditary, autosomal dominant, form of hepatic porphyria manifested by recurrent attacks of abdominal pain, gastrointestinal dysfunction, and neurologic disturbances, and by excessive amounts of δ-aminolevulinic acid and porphobilinogen in the urine; it is due to an abnormality of pyrrole metabolism. Called also intermittent acute porphyria.
congenital erythropoietic porphyria (CEP) a form of erythropoietic porphyria, with cutaneous photosensitivity leading to mutilating lesions, hemolytic anemia, splenomegaly, excessive urinary excretion of uroporphyrin and coproporphyrin, and invariably erythrodontia and hypertrichosis. Called also Günther disease.
porphyria cuta´nea tar´da (PCT) the most common form of porphyria, characterized by cutaneous photosensitivity that causes scarring bullae, discoloration, growth of facial hair, and sometimes sclerodermatous thickenings and alopecia; it is frequently associated with alcohol abuse, liver disease, or hepatic siderosis. Urinary levels of uroporphyrin and coproporphyrin are increased. There are two main types: an autosomal dominant (or familial ) form in which activity of the affected enzyme is reduced to half normal in liver, erythrocytes, and fibroblasts; and a sporadic (but probably also familial) form in which the reduction is confined to the liver. Both types are believed to be heterozygous and clinical expression occurs in adulthood, precipitated by disease or environmental factors. A more severe homozygous form begins in childhood and is called hepatoerythropoietic porphyria.
erythropoietic porphyria porphyria in which excessive formation of porphyrin or its precursors occurs in bone marrow erythroblasts; the group includes congenital erythropoietic porphyria and erythropoietic protoporphyria.
hepatic porphyria porphyria in which the excess formation of porphyrin or its precursors is found in the liver; it includes acute intermittent porphyria, variegate porphyria, and hereditary coproporphyria.
hepatoerythropoietic porphyria (HEP) a severe homozygous form of porphyria cutanea tarda believed to result from an autosomal dominant defect in the same enzyme as is affected in porphyria cutanea tarda; it is clinically identical to that disease but onset is in early childhood and enzyme activity in liver, erythrocytes, and fibroblasts is virtually absent.
intermittent acute porphyria acute intermittent porphyria.
porphyria variega´ta (variegate porphyria (VP)) a hereditary, autosomal dominant, type of hepatic porphyria characterized by chronic cutaneous manifestations, notably extreme mechanical fragility of the skin, particularly areas exposed to the sunlight, and by episodes of abdominal pain and neuropathy. There is typically an excess of coproporphyrin and protoporphyrin in the bile and feces.

in·ter·mit·tent a·cute por·phyr·i·a (IAP),

[MIM*176000]
porphyria caused by hepatic overproduction of δ-aminolevulinic acid, with greatly increased urinary excretion of it and of porphobilinogen, and some increase of uroporphyrin, due to a deficiency of porphobilinogen deaminase; characterized by intermittent acute attacks of hypertension, abdominal colic, psychosis, and polyneuropathy, but with no photosensitivity; autosomal dominant inheritance, caused by mutation in the human porphobilinogen deaminase gene on 11q24; exacerbation caused by ingestion of certain drugs (for example, barbiturates).

acute intermittent porphyria (AIP)

an autosomal-dominant, genetically transmitted metabolic hepatic disorder characterized by acute attacks of neurological dysfunction that can be started by environmental or endogenous factors. Women are affected more frequently than men, and attacks often are precipitated by starvation or severe dieting, alcohol ingestion, bacterial or viral infections, and a wide range of pharmaceutical products. Any part of the nervous system can be affected, and an initial common effect is mild to severe abdominal pain. Other effects can include tachycardia, hypertension, hyponatremia, peripheral neuropathy, and organic brain dysfunction marked by seizures, coma, hallucinations, and respiratory paralysis. A frequent diagnostic factor is a high level of porphyrin precursors in the urine, which usually increases during periods of acute attacks. Treatment is generally symptomatic, with emphasis on respiratory support, beta-blockers, and pain control. Education of the patient focuses on environmental factors, particularly medications such as barbiturates, that are known to cause an onset of symptoms, as well as avoidance of alcohol, sunlight, and skin trauma. A high-carbohydrate diet is reported to reduce the risk of acute attacks because glucose tends to block the induction of hepatic gamma-aminolevulinic acid synthetase, an enzyme involved in the porphyrias. See also porphyria.

acute intermittent porphyria

An autosomal dominant MIM 176000 condition caused by a deficiency of porphobilinogen deaminase (hydroxymethylbilane synthase [EC 4.3.1.8]), resulting in overproduction of delta-aminolevulinic acid.
 
Clinical findings
Abdominal colic, constipation, fever, leukocytosis, postural hypotension, peripheral neuritis, polyneuropathy, paraplegia, urinary retention, respiratory paralysis, behavioural changes and episodic psychosis (patients are often misdiagnosed as having psychiatric disorders), photosensitivity; symptoms are worse with barbiturates.
 
Triggering factors
The four Ms: medication, menstruation, malnutrition, maladies.

Lab
Increased delta-aminolevulinic acid, urine porphobilinogen.
 
Management
Haematin and haeme arginate, high-carbohydrate diet or IV glucose; narcotics for pain + laxatives; avoid drugs that trigger disease—e.g., valproate, tamoxiphen, cocaine, oral contraceptives; neurontin for seizures.

Prognosis
Mostof patients (60% to 80%) have only one acute attack during their lives.

acute intermittent porphyria

Hematology An AD condition caused by a deficiency of porphobilinogen deaminase, resulting in overproduction of δ-aminolevulinic acid Clinical Recurrent abdominal colic, constipation, fever, leukocytosis, postural hypotension, peripheral neuritis, polyneuropathy, paraplegia, urinary retention, respiratory paralysis, behavioral changes and episodic organic psychosis, photosensitivity; worse with barbiturates Lab ↑ δ-aminolevulinic acid, urine porphobilinogen

in·ter·mit·tent a·cute por·phyr·i·a

(IAP) (in'tĕr-mit'ĕnt ă-kyūt' pōr-fir'ē-ă)
Disorder caused by the hepatic overproduction of δ-aminolevulinic acid, with a great increase in urinary excretion of it and of porphobilinogen, due to a deficiency of porphobilinogen deaminase; characterized by intermittent acute attacks of hypertension, abdominal colic, psychosis, and polyneuropathy, but with no photosensitivity; exacerbated by ingestion of certain drugs (e.g., barbiturates).
Synonym(s): acute intermittent porphyria, acute porphyria.

Acute intermittent porphyria

An inherited disease affecting the liver and bone marrow. The liver overproduces a specific acid and the disease is characterized by attacks of high blood pressure, abdominal colic, psychosis, and nervous system disorders.
References in periodicals archive ?
Nerve function and dysfunction in acute intermittent porphyria.
A retrospective study of a patient with homozygous form of acute intermittent porphyria.
A urine sample from a patient with acute intermittent porphyria in long-term remission, but with continuing excretion of PBG, had a PBG concentration of 25 [micro]mol/L.
The extracted SRM chromatogram obtained from a specimen from a patient with acute intermittent porphyria in which the calculated PBG concentration was 110 mg/24 h is shown in Fig.
An emission peak at ~621 nm rather than at ~635 nm was reported in acute attacks of either coproporphyria (9,24) or acute intermittent porphyria (24).
Acute intermittent porphyria (AIP) is an autosomal dominant, inborn error of the metabolism of heme biosynthesis caused by partial deficiency of hydroxymethylbilane synthase (HMBS).
AMT also has a product pipeline of several gene therapy products in development for hemophilia B, Duchenne muscular dystrophy, acute intermittent porphyria, Parkinson's disease, and SanfillipoB.
Because AMT's technology can be applied equally to a wide range of other genetic diseases, the success of Glybera(R) would validate AMT's approach for its other pipeline products, targeting a range of orphan diseases and diseases with large patient populations, in each case where there is high unmet medical need, including Parkinson's disease, hemophilia, Duchenne muscular dystrophy (DMD) and acute intermittent porphyria (AIP).
Except for the use of erythrocyte porphobilinogen deaminase activity to confirm the diagnosis of acute intermittent porphyria (AIP), [1] enzyme assays have little to offer in the routine investigation of these diseases.
3 million grant to the AIPGENE consortium, of which AMT is a member, for the development of a gene therapy product for Acute Intermittent Porphyria (AIP).
Additional investigation by HPLC fractionation of urine and fecal porphyrins led to a diagnosis of acute intermittent porphyria (AIP).
Highlights - Glybera(R) Marketing Authorisation Application submitted to European Medicines Agency (EMA, formerly known as EMEA); - EMA commenced formal review of Glybera(R) dossier on January 20, 2010; - EMA grants orphan drug designation for AMT's Acute Intermittent Porphyria ("AIP") program; - EMA grants orphan drug designation for AMT's Duchenne Muscular Dystrophy ("DMD") program; - SenterNovem awards EUR 4 million investment credit for the development of AMT's DMD program; - Raised EUR 5 million convertible loan notes, which convert into ordinary shares at EUR 3.

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