CD-ROM Today 1996 January/CD-ROM Today 1996 January.iso/dp/0413/04130.txt

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$Unique_ID{BRK04130}
$Pretitle{}
$Title{Porphyria, Erythropoietic Protoporphyria}
$Subject{Porphyria Erythropoietic Protoporphyria Porphyria EPP}
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Copyright (C) 1987, 1988, 1990 National Organization for Rare Disorders, Inc.

322:
Porphyria, Erythropoietic Protoporphyria

** IMPORTANT **
It is possible the main title of the article (Erythropoietic
Protoporphyria) is not the name you expected.  Please check the SYNONYMS
listing to find the alternate names and disorder subdivisions covered by
this article.

Synonyms

     Porphyria
     EPP

General Discussion

** REMINDER **
The information contained in the Rare Disease Database is provided for
educational purposes only.  It should not be used for diagnostic or
treatment purposes.  If you wish to obtain more information about this
disorder, please contact your personal physician and/or the agencies listed
in the "Resources" section of this report.


Erythropoietic Protoporphyria (EPP) is inherited as an autosomal dominant
trait and is primarily a bone marrow disorder.  Ferrochelatase is the
deficient enzyme, and there is an accumulation of protoporphyrin in the bone
marrow, red blood cells and sometimes in the liver.  Excess protoporphyrin is
excreted by the liver into the bile, which in turn enters the intestine and
is excreted in the feces.  There are no urinary abnormalities.  The diagnosis
is established by finding increased protoporphyrin in the red blood cells,
plasma and feces.

The Porphyrias are a group of at least seven disorders.  The common
feature in all porphyrias is the excess accumulation in the body of
"porphyrins" or "porphyrin precursors."  These are natural chemicals that
normally do not accumulate in the body.  Precisely which one of these
porphyrin chemicals builds up depends upon the type of porphyria that a
patient has.

Porphyrias can also be classified into two groups:  the "hepatic" and
"erythropoietic" types.  Porphyrins and related substances originate in
excess amounts from the liver in the hepatic types, and mostly from the bone
marrow in the erythropoietic types.

The porphyrias with skin manifestations are sometimes called "cutaneous
porphyrias."  The "acute porphyrias" are characterized by sudden attacks of
pain and other neurological manifestations.  These "acute symptoms can be
both rapidly-appearing and severe.  An individual may be considered in a
"latent" condition if he or she has the characteristic enzyme deficiency, but
has never developed symptoms.  There can be a wide spectrum of severity
between the "latent" and "active" cases of any particular type of this
disorder.

The symptoms and treatments of the different types of porphyrias are not
the same.  For more information on the other types of porphyria, choose
"porphyria" as your search term in the Rare Disease Database.

Symptoms

In Erythropoietic Protoporphyria, swelling, burning, itching, and redness of
the skin may appear during or immediately after exposure to sunlight,
including sunlight through window glass.  Usually, these symptoms subside in
12 to 24 hours and heal without significant scarring or discoloration of the
skin.  Occasionally, the skin problems occur only after extended sunlight
exposure.  The skin lesions may progress to a chronic stage persisting for
weeks and healing with a superficial scar.  However, blistering and scarring
is less common than in other types of "cutaneous" porphyria.  Skin
manifestations generally begin during childhood.  They are more severe in the
summer and can recur throughout life.  Other manifestations may include
gallstones containing protoporphyrin, and occasionally, severe liver
complications.

The symptoms of porphyria generally arise from effects on the nervous
system and/or the skin.  Sometimes, the cause of the nervous system symptoms
is not clear, and proper diagnosis is delayed.  Skin manifestations can
include burning, blistering and scarring of sun-exposed areas.

Porphyria Cutanea Tarda is the only type of porphyria that can be either
acquired or inherited.  All other types of Porphyria are caused by genetic
factors.  Environmental factors such as drugs, chemicals, diet and sun
exposure can, depending on the type of the disorder, greatly influence the
severity of symptoms.

The terms "porphyrin" and "porphyria" are derived from the Greek word
"porphyrus," meaning purple.  Urine from some porphyria patients may be
reddish in color due to the presence of excess porphyrins and related
substances, and the urine may darken after being exposed to the light.

Causes

Erythropoietic Protoporphyria involves an inborn error of metabolism
inherited as a dominant trait.  (In autosomal dominant disorders, a single
abnormal gene, contributed by either parent, "overrides" the normal gene
contributed by the other parent causing disease.  Individuals with one
affected parent have a 50% chance of inheriting the disorder.  Males and
females will be affected in equal numbers.)

Environmental factors may include drugs, chemicals, diet and sun
exposure.  Depending on the type of porphyria, these factors can greatly
influence the severity of symptoms.

Affected Population

Erythropoietic Protoporphyria usually begins in childhood.  The intensity of
symptoms may increase in summer and fall.  This disorder may affect males and
females in equal numbers.

Related Disorders

The Porphyrias are a group of related disorders.  For more information on
each of the following types of the disease, choose "porphyria" as your search
term in the Rare Disease Database.

ALA-D Porphyria is a recently-described form of acute porphyria inherited
as an autosomal recessive trait.  It is apparently extremely rare.  There is
a deficiency of the enzyme delta-aminolevulinic acid dehydratase (ALA-D) and
increased excretion of ALA in the urine of patients with this type of
porphyria.

Acute Intermittent Porphyria is a hereditary, possibly metabolic, usually
asymptomatic disorder (latent).  It may possibly be provoked into active
disease by the administration of certain drugs, notably barbiturates,
sulfonamides, and estrogenic compounds.

Congenital Erythropoietic Porphyria (CEP) is a hereditary disorder due to
an inborn error of metabolism, and manifested in infancy.  Faulty conversion
of the enzyme PBG to uroporphyrinogen in erythroid cells of bone marrow, red
blood cells, plasma, urine and feces leads to this type of Porphyria.
Increased porphyrins also may be found in plasma, urine, feces, teeth and
bones.

Porphyria Cutanea Tarda (PCT) can be either an acquired or inherited type
of Porphyria.  It may become acute due to exposure to chronic alcoholism,
barbiturates or other chemicals, cirrhosis of the liver, or a hepatic tumor.
It may also stem from a nutritional disorder.

Hereditary Coproporphyria (HCP) is a latent type of Porphyria with
attacks usually precipitated by exposure to drugs such as barbiturates,
tranquilizers, anticonvulsants, and estrogens.

Variegate Porphyria (VP) is a hereditary type of Porphyria due to an
inborn error of metabolism.  Precipitating or aggravating factors may include
exposure to barbiturates, sulfonamides, general anesthetics, excessive
amounts of ethanol, and estrogens.

Therapies:  Standard

Treatment for Erythropoietic Protoporphyria (EPP) with the orphan drug Beta
Carotene often improves sunlight tolerance, but does not lower porphyrin
levels.  Cholestyramine may lower porphyrin levels in some patients.  Some
carriers of the gene for this disease have no symptoms, and may occasionally
have normal porphyrin levels.

Patients with EPP may develop liver abnormalities, due to excess deposits
of protoporphyrin in that organ.  Total avoidance of certain drugs including
barbiturates, sulfonamides, and estrogen compounds is suggested.  It is
important to note that a patient with EPP never develops any other types of
porphyria, although some treatments may be similar.  Avoidance of alcohol is
also strongly suggested as alcohol seems to increase severity of
photosensitivity in this disorder.

The orphan drug Hematin (an intravenous drug) is very potent in
suppressing acute attacks of the disease.  It is usually given only after a
trial of glucose therapy.  Attention should be given to salt and water
balance during treatment.

Many types of drugs such as aspirin and certain antibiotics are believed
to be safe in patients with some types of porphyria.  Recommendations about
drugs for certain types of the disorder are based on experience with the
porphyria patients in whom attacks have been caused by drugs and by tests in
animals.  Since many commonly used drugs have not been tested, they should be
avoided if at all possible.  If a question of drug safety arises, a physician
or medical center specializing in porphyria should be contacted.  A list of
these institutions may be procured from the American Porphyria Foundation
(see Resources).

Pregnancy is tolerated much better than was formerly believed.  Many
patients have a few reservations about family planning.  For those who do,
genetic counseling may be useful.

Wearing a Medic Alert bracelet is advisable in patients who have had
attacks, but is probably not warranted in most latent cases.

Therapies:  Investigational

New treatments for several types of porphyria are under investigation.  For
the most updated information on research, please contact the organizations
listed in the Resources section.

This disease entry is based upon medical information available through
March 1990.  Since NORD's resources are limited, it is not possible to keep
every entry in the Rare Disease Database completely current and accurate.
Please check with the agencies listed in the Resources section for the most
current information about this disorder.

Resources

For more information on Erythropoietic Protoporphyria, please contact:

     National Organization for Rare Disorders (NORD)
     P.O. Box 8923
     New Fairfield, CT  06812-1783
     [phone]

     American Porphyria Foundation
     P.O. Box 22712
     Houston, TX  77227
     [phone]

     Porphyria Support Group
     4 Eve Road
     Leytonstone, London, England
     E11 3JE
     Tel:  [phone]

     National Digestive Diseases Information Clearinghouse
     Box NDDIC
     Bethesda, MD  20892
     [phone]

For information on genetics and genetic counseling referrals, please
contact:

     March of Dimes Birth Defects Foundation
     1275 Mamaroneck Avenue
     White Plains, NY  10605
     [phone]

     Alliance of Genetic Support Groups
     35 Wisconsin Circle, Suite 440
     Chevy Chase, MD  20815
     (800) 336-GENE
     [phone]

References

American Porphyria Foundation brochure, "Common Questions About Porphyria."