CD-ROM Today (UK) (Spanish) 15/CDRT.iso/dp/0413/04132.txt

Text File | 1994-01-17 | 12KB | 272 lines

$Unique_ID{BRK04132}
$Pretitle{}
$Title{Porphyria, Variegate}
$Subject{Porphyria Variegate Porphyria VP Porphyria Cutanea Tarda Hereditaria
Mixed Hepatic Porphyria South African Genetic Porphyria Porphyria Hepatica}
$Volume{}
$Log{}

Copyright (C) 1987, 1988, 1990, 1991, 1993 National Organization for Rare
Disorders, Inc.

324:
Porphyria, Variegate

** IMPORTANT **
It is possible the main title of the article (Variegate Porphyria) 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
     VP
     Porphyria Cutanea Tarda Hereditaria
     Mixed Hepatic Porphyria
     South African Genetic Porphyria
     Porphyria Hepatica

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.


Variegate Porphyria (VP), a form of hepatic porphyria, is most common in
the South African white population and is much less frequent elsewhere.  It
is an autosomal dominant disorder and may produce acute attacks (as in acute
intermittent porphyria) as well as skin photosensitivity.  This form of
porphyria is also due to an enzyme deficiency.

The diagnosis may be made by finding excess coproporphyrin in urine and
both coproporphyrin and protoporphyrin in feces.  In patients with
photosensitive skin changes alone, it is important to distinguish Variegate
Porphyria or hereditary coproporphyria (HCP) from porphyria cutanea tarda
(PCT), because treatment by phlebotomy or low-dose chloroquine is not
successful in VP and HCP.  Acute attacks are managed and may be prevented as
in AIP.

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

Variegate Porphyria shows no symptoms during the latent phase of the
disorder.  During an acute attack, a patient may experience abdominal colic,
severe vomiting, or sweating.

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.

Because this disease can mimic a host of other more common conditions,
its presence is often not suspected.  On the other hand, the diagnosis of
this and other types of porphyria is sometimes made incorrectly in patients
who do not have porphyria, particularly if improper laboratory tests are
carried out.  The finding of increased levels of delta-aminolevulinic acid
(ALA) in urine establishes that one of the "acute" porphyrias is present.

When a patient is diagnosed as having VP, relatives should be examined as
well.  Latent cases so identified can then avoid agents known to cause
attacks.

Causes

Variegate Porphyria (VP) is a hereditary, non-x-linked dominant disorder, due
to an inborn metabolic error (a deficiency of protoporphyrinogen oxidase).
Precipitating factors may include exposure to barbiturates, sulfonamides,
general anesthetics, excessive amounts of alcohol, and/or estrogens.

Human traits including the classic genetic diseases, are the product of
the interaction of two genes for that condition, one received from the father
and one from the mother.  In dominant disorders, a single copy of the disease
gene (received from either the mother or father) will be expressed
"dominating" the normal gene and resulting in appearance of the disease.  The
risk of transmitting the disorder from affected parent to offspring is 50%
for each pregnancy regardless of the sex of the resulting child.

Environmental factors that can precipitate attacks of Variegate Porphyria
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

Variegate Porphyria (VP) may begin between the ages of ten to thirty years.
It is particularly common in the white population of South Africa, and 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 form 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, and
red blood cells leads to of this type of Porphyria.  Increased porphyrins
also may be found in plasma, urine and feces.  Porphyrins are also deposited
in the 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.

Erythropoietic Protoporphyria (EPP) is a hereditary type of Porphyria
marked by an accumulation of protoporphyrin in the bone marrow, red blood
cells and sometimes 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 red blood cells, plasma and feces.

Therapies:  Standard

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 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.

Dr. Karl E. Anderson of the University of Texas Medical Branch,
Galveston, TX, 77550, has received orphan drug designation for Histrelin, a
drug to treat various types of Porphyria.

Research is underway on the Finnish product Normasang (heme arginate).
Dr. Karl Anderson of The University of Texas Medical Branch will be directing
clinical studies in the United States.  Patients are needed to participate in
this research.  People interested in this study should have their physician
contact:

     Dr. Karl Anderson
     Ewing Hall (J-09)
     University of Texas Medical Branch
     700 Strand St.
     Galveston, TX  77555
     [phone]

This disease entry is based upon medical information available through
January 1993.  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 Variegate Porphyria, 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."