Porphyria Acquired

The porphyrias are a group of disorders due to abnormalities in the pathway of biosynthesis of heme they can be genetic or acquired. They are not prevalent, but it is important to consider them in certain circumstances (eg, in the differential diagnosis of abdominal... 

There are a large number of hereditary or acquired disturbances of porphyrin synthesis, known as porphyrias, some of which can cause severe clinical pictures. Several of these diseases lead to the excretion of heme precursors in feces or urine, giving them a dark red color. Accumulation of porphyrins in the skin can also occur, and exposure to light then causes disfiguring, poorly healing blisters. Neurological disturbances are also common in the porphyrias. 

Most of the adverse reactions associated with the use of the intravenous barbiturates are predictable and therefore can be controlled or avoided. Some reactions, such as hypersensitivity, are entirely unpredictable. Particularly patients with asthma, urticaria, or an-gioedema may acquire allergic hypersensitivity to the barbiturates. Acute intermittent porphyria is an absolute contraindication to the use of barbiturates. 

Porphyrias are caused by inherited (or occasionally acquired) defects in heme synthesis, resulting in the accumulation and increased excretion of porphyrins or porphyrin precursors (see Summary Figure 21.7). With the exception of congenital erythropoietic porphyria, which is a genetically recessive disease, all porphyrias are inherited as autosomal dominant disorders. The mutations that cause the porphyrias are heterogenous (not all are at the same DNA locus), and nearly every affected family has its own mutation. Each porphyria results in the accumulation of a unique pattern of intermediates caused by the deficiency of an enzyme in the heme synthetic pathway. 

The porphyrias. The human body does not use all of the porphobilinogen produced, and a small amount is normally excreted in the urine, principally as coproporpyrins (Fig. 16-5). In a number of hereditary and acquired conditions blood porphyrin levels are elevated and enhanced urinary excretion (porphy-... 

Inborn metabolic diseases that interfere with heme biosynthesis are called porphyrias. Porphyrias have a variety of symptoms. A deficiency in the enzyme responsible for the condensation of porphobilinogen to the 4-membered ring system leads to a condition called acute intermittent porphyria, which is characterized by occasional episodes of abdominal pain and psychiatric symptoms. Defects in the later enzymes of the pathway lead to an excess accumulation of the uroporphobilinogens in the tissues, where they cause a variety of symptoms, including hairy skin, skeletal abnormalities, light sensitivity, and red urine. Individuals with this disease are still anemic—a condition that can be alleviated somewhat by the heme acquired from drinking blood. This combination of traits sounds like the werewolf and vampire legends of Europe, which may have their base in this rare biochemical disease. 

Inherited defects or porphyrine biosynthetic enzymes can cause the accumulation of pathway intermediates that cannot be converted anymore with sufficient velocity. Various genetic forms of porphyria have been reported and result in liver toxicity, neurological damage and photosensitivity (75). Acquired forms of porphyria can be caused by a variety of toxic and pharmacologic agents. 

Bleiberg J, Wallew M, Brodkin K et al. Industrially acquired porphyria. Arch Dermatol 1964 89 793-7. 

The porphyrias are a group of disorders caused by abnormalities in heme biosynthesis. They are inherited and acquired disorders characterized by excessive accumulation and excretion of porphyrins or their precursors. Defects in any one of the eight enzymes involved in heme biosynthesis may cause inherited porphyrin-related disorders (Figure 29-9). Porphyrins have a deep red or purple color (Greek porphyra = purple). Porphyrins are... 

Porphyrias are inherited or acquired disorders caused by a deficiency of enzymes in the heme biosynthetic pathway. Porphyrin is synthesized in both the erythroblasts and the liver, and either one may be the site of a disorder. Congenital erythropoietic pOTjdtyria, for example, prematurely destroys eythrocytes. This disease results from insufficient cosynthase. In this porphyria, the synthesis of the required amount of uroporphyrinogen III is accompanied by the formation of very large quantities of uroporphyrinogen I, the useless symmetric isomer. Uroporphyrin I, coproporphyrin I, and other symmetric derivatives also accumulate. The urine of... 

Porphyria—A group of disorders involving heme biosynthesis, characterized by excessive excretion of porphyrins or their precursors may be inherited or may be acquired, as from the effects of certain chemical agents. 

Several types of porphyria can be worsened by circulating metabolites following exposure to UVR. In particular, congenital and acquired porphyria cutanea tarda are typically characterised by skin lesions, in particular on the hands, with increased skin fragility and vesicular, bullous and ulcerative lesions on light exposed skin. Similar lesions can also be induced by simultaneous exposure to UVR and contact/adminis-tration with porphyrinogenic substances, e.g. hex-achlorobenzene, tetrachlorodibenzo-p-dioxin, etc. 

Clinical Pathology of Porphyria Porphyria Hepatica Acquired Porphyria... 

Cam, C. and Nigogosyan, G. 1963. Acquired toxic porphyria cutanea tarda due to... 

Nordman Ch, Hernberg S, Nikkanen J, Rykanen A (1973) Blood lead levels and erythrocyte (5-aminolevulinic acid dehydratase activity in people living around a secondary lead smelter. Work Environ Health 10 19-25 Ockner RK, Schmid R (1961) Acquired porphyria in man and rat due to hexachlo-robenzene intoxication. Nature 189 499... 

On the subject of skin photosensitivity it is fitting to mention porphyria, which belongs to a group of inherited or acquired disorders of certain enzymes in the heme biosynthetic pathway. The main problem with porphyria is the accumulation of porphyrins, which are the heme precursors in the body. While porphyrins are non-toxic at biologically relevant concentrations, they become toxic to tissue at high concentration. Deficiency in the enzymes of the porphyrin biosynthetic pathway leads to insufficient production of heme, which plays a central role in cellular metabolism, and accumulation of porphyrins. The high concentration of porphyrins manifests itself by either neurological complications or by skin problems. The presence of porphyrins in the skin in porphyria patients is therefore akin to skin photosensitivity in PDT. 

A type of porphyrin molecule having methyl and propionate side groups (unlike uroporphyrin, which has acetate and propionate side groups, and protoporphyrin, which has methyl, vinyl and propionate side groups). Excess coproporphyrins are found in the urine and faeces in many types of porphyria and in acquired porphyrinurias (e.g. lead poisoning). 

A group of disorders in which there is disturbance of porphyrin biosynthesis resulting in increased blood and tissue levels of porphyrins or their precursors. Most types of porph3rria are hereditary while one (symptomatic cutaneous hepatic porphyria) is acquired. The porphyrias can be classified into several groups depending upon whether the basic abnormality is in the liver or the erythropoietic system or both ... 

An acquired form of hepatic porphyria which can be caused by severe liver disease or toxins. It is accompanied by an increased urinary excretion of porphyrins, especially uroporphyrins. Hirsutism and cutaneous lesions are among the clinical symptoms. 

B. I Porphyria is an inherited or acquired block in the enzymatic steps that govern heme syn-thesis, resulting in overproduction of heme precursors above the block. 

The porphyrias are a group of diseases in which disturbances of porphyrin metabolism occur either as inherited or acquired abnormalities. They are classified into the so-called erythropoietic and hepatic forms according to the chemical evidence of the primary site of the metabolic defect [63], and it is the second, hepatic group which mainly concerns us here in this discussion on neuropathies. 

In three of the hereditary hepatic porphyrias, acute intermittent porphyria, porphyria variegata [64], and hereditary coproporphyria [65, 66] neurological abnormalities are recognized, of varying character and severity, and similar changes are described in a minority of cases of acquired hepatic porphyrias. 

For the neurologist, the main interest lies in acute intermittent porphyria in which psychotic features coexist with an acute or subacute peripheral neuropathy and abdominal pain. Similar features are less frequent and severe in the other forms of hepatic porphyria, both inherited and acquired. 

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