Porphyria Educational Services
PORPHYRIA EDUCATIONAL SERVICES BULLETIN Vol. 1 No. 18 May
2, 1999
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.