congenital erythropoietic porphyria


porphyria

 [por-fēr´e-ah] a genetic disorder characterized by a disturbance in porphyrin" >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" >hemes, which in turn combine with specific proteins to form hemoproteins" >hemoproteins. hemoglobin" >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.

con·gen·i·tal e·ryth·ro·poi·et·ic por·phyr·i·a (CEP),

[MIM*263700] enhanced porphyrin formation by erythroid cells in bone marrow, leading to severe porphyrinuria, often with hemolytic anemia and persistent cutaneous photosensitivity; caused by a deficiency of uroporphyrinogen III cosynthetase; autosomal recessive inheritance, caused by mutation in the uroporphyrinogen III synthase gene (UROS) on chromosome 10q; there is an overproduction of type I porphyrin isomers.

congenital erythropoietic porphyria

A rare (less than 100 cases described) autosomal recessive condition caused by uroporphyrinogin III cosynthetase deficiency.
 
Clinical findings
Severe photosensitivity with development of vesicles and bullae in skin that heal slowly and leave pigmented scars; photomutilation of fingers and acral parts; hypertrichosis; porphyrin deposition in teeth, which may cause them to become red, yellow, or brown; and haemolytic anaemia.
 
Lab
Normochromic, normocytic anaemia, porphyrin overload.
 
Management
Avoid sunlight; splenectomy, hypertransfusion plus chelation therapy to minimise iron overload; activated charcoal to bind porphyrins.
Prognosis
A normal lifespan is possible with strict avoidance of sunlight; the usual life expectancy is 40 to 60.

con·gen·i·tal e·ryth·ro·poi·et·ic por·phyr·i·a

(kŏn-jen'i-tăl ĕ-rith'rō-poy-et'ik pōr-fir'ē-ă) Enhanced porphyrin formation by erythroid cells in bone marrow, leading to severe porphyrinuria, often with hemolytic anemia and persistent cutaneous photosensitivity; caused by a deficiency of uroporphyrinogen III cosynthetase.