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Porphyria Educational Services

FOCUS: The Erythropoietic System Porphyrias EPP & CEP

Among the rarer forms of porphyria are those of EPP [Erythropoetic Protoporphyria] and the CEP [Congenital Erythropoietic Porphyria].

In the EPP there is an involvement of a defect in the hepatic cells, while in both the EPP and CEP the cause of the porphyria is due to the a major enzymatic abnormality in the erythropoietic system.

Before we begin, let us define some of the terms used. The prefix "erythro" is a combing word meaning "red". "Erythrocytes" are red blood cells. So we are talking "red". "Enzymes" are a protein that causes chemical reactions in living matter. Enzymes affect the reactions that take place within the cells of our body.

In EPP the problem lies in the overproduction of protophyrin in the red blood cells as well as in the liver cells. Other names that it has been known as are "protoporphyria" and "erythrohepatic porphyria."

EPP is inherited as an autosomal dominant trait. The EPP is though to be due to partial absence of the mitochrondial enzyme ferrochelatase, which is also called the heme synthetase.

The most prominent feature of this disorder is the photosensitivity. This is thought to be due to the increased levels of plasma protoporphyrin. Excess plasma protoporphyrin reults from the overproduction by the hepatocytes alogn with the erythrocytes.

Unlike the hepatic porphyrias, protoporphyria [EPP] usually occurs in children younger than four years of age. Whereas females are mostly active in the hepatic forms, it is the males that are mostly affected with the EPP.

Symptomology of EPP includes burning and itching which are predominatly triggered by sunlight. The symptoms are often acoompanied by edema, erythema [an abnormal increase int the red blood cells], and /or urticaria [a skin eruption marked by transient wheals of varying shapes and sizes]. 0ther symptoms which are less frequent are blisters and skin ulcers.

The lesions will have reoccurrence as a result of chronic sun exposure which will lead to scarring, altered pigmentation, lichenification, and the premature aging of the skin. Lichenification is a thickening and hardening of the skin which often results from irritation caused by repeated scratching of a lesion that is itching.

Another aspect of EPP is that there are increased amounts of protoporphyrin deposited in the liver. There are as a rule, mild liver function abnormalities.
Cirrhosis, liver failure, liver transplantation, and hepatosplenomegaly are also noted as well.

Some EPP patients have amanifestation of gallstones. About half of the EPP patients have a mild hypochromic, microcytic anemia. Some hemolysis may also be present.

A more severe form of protoporphyria occurs if both parents are heterozygous. The ofspring inherit two defective genes. As of 1996 there were at least eleven different EPP mutations found. In EPP the majority of carriers are asymptomatic.

The diagnosis of EPP is usually made by combining the history and familial occurence and the increased levels of stool and erythrocyte protoporphyrin. In the testing of the samples the erythrocytes flouoresce on exposure to the Soret band.

Prevention of EPP symptoms is the avoidance of sunlight.. The avoidance of sun will help to prevent the irreversible scarring. Intervention therapy is the ingestion of beta carotene. What the beta carotene does is to help with the reaching of blood levels high enough to diminish photosensitivity. Sometimes the use of pyridoxine has been advocated, however the drug does not alter porphyrin metabolsm.

Now we will move to another form of porphyria, that being CEP.

The CEP form of porphyria is also known as Gunther's Disease. CEP is also inherited.
I ti is an autosomal recessive trait. The emzyme responsible for this disorder is a deficiency of the uroporphyringon II synthase.

In CEP the excess porphyrin in the boidy causes staining of the bones and teth which is known as erythrodontia. In addition the symptoms of CEP include hemolysis, dark urine, and the typical photosensitivity.

CEP is usually identified early in infancy.

Repeated vesiculation, scarring, and mutilation following exposure to sunlight are key exacerbations of CEP.

0ral sorbents like cholestyramine and charcoal are interevention therapies advocated for CEP whereas they decrease reabsorption of porphyrins from the intestines.

All too often in CEP premature death occurs. Bone marrow transplantation has been successful in some patients. However in CEP patients usually die from opportunistic infection due to the CEP patient's weakness and inability to fight off viruses and bacteria.

Research is ongoing in findings solutions. Gene therapy for porphyria has been quite successful in cell cluture and animal models, but these therapies have not yet reached the human clinical trials which taks many years to accomplished before they are finally approved for routine therapy.

A noted researcher in the area of EPP is Dr. Michelene Matthews-Ross MD at Harvard.