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

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 ?
Acute intermittent porphyria (AIP) is the most common of the acute hepatic porphyrias, and results from partial deficiency of porphobilinogen deaminase, the third enzyme of the haem synthetic pathway [Badminton and Elder, 2002].
The primary endpoint was reduction relative to placebo in the annualised rate of composite porphyria attacks, defined as those requiring hospitalisation, urgent healthcare visit, or hemin administration at home, in patients with acute intermittent porphyria (AIP, the most common subtype of AHP) over six months.
Because fecal total porphyrins were moderately increased at 374 nmol/g dry weight (reference value <200 nmol/g) consisting of proto- and coproporphyrin with a trace of uroporphyrin on TLC, a diagnosis of acute intermittent porphyria (AIP) was considered.
ENVISION, a randomized, double-blind, placebo-controlled trial, enrolled 94 patients with AHP (including 89 with genetically-confirmed acute intermittent porphyria [AIP], the most common subtype of AHP), at 36 study sites in 18 countries around the world, and is the largest ever interventional study conducted in AHP.
Acute intermittent porphyria (AIP), the most common porphyria affecting the nervous system, typically presents with neurovisceral crises followed by a motor neuropathy.
Acute intermittent porphyria (AIP) [1] (MIM 176000) is a low-penetrance, autosomal dominant disorder caused by decreased activity of the third enzyme in the pathway of heme biosynthesis, hydroxymethylbilane synthase (HMBS).
Results showed that basal ALAS1 messenger RNA, aminolevulinic acid, and porphobilinogen levels were associated with disease activity, with higher levels noted in those with recurrent attacks, confirming the central importance of liver ALAS1 induction and ALA and PBG in the pathophysiology of acute intermittent porphyria.
Acute intermittent porphyria presenting solely with psychosis: A case report and discussion.
The 3 most common acute porphyrias are hereditary coproporphyria, variegate porphyria, and acute intermittent porphyria, all inherited as autosomal dominant disorders.
The Phase 1 study of givosiran (Part C) was conducted as a randomized, double-blind, placebo-controlled study in 17 patients with acute intermittent porphyria who experienced recurrent porphyria attacks.
Diagnosis of 65 cases of VP, 36 cases of PCT, 6 of acute intermittent porphyria (AIP), 3 of erythropoietic protoporphyria (EPP), 5 of X-linked protoporphyria and 1 of congenital erythropoietic porphyria was confirmed.

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