CD-ROM Today 1996 January/CD-ROM Today 1996 January.iso/dp/0412/04127.txt

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$Title{Porphyria, Acute Intermittent}
$Subject{Porphyria, Acute Intermittent Porphyria AIP}
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Copyright (C) 1987, 1988, 1990, 1991, 1992, 1993 National Organization
for Rare Disorders, Inc.

318:
Porphyria, Acute Intermittent

** IMPORTANT **
It is possible the main title of the article (Acute Intermittent
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
     AIP

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.


Acute Intermittent Porphyria (AIP) is one of a group of hereditary
hepatic Porphyrias.  It is inherited as an autosomal dominant trait.  The
deficient enzyme is porphobilinogen deaminase (PBG-D), also known as
uroporphyrinogen I-synthase.  This enzyme deficiency by itself is not
sufficient to produce symptoms of the disease.  Other factors must also be
present such as hormones, drugs and dietary changes which trigger the
appearance of symptoms.

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.  In the hepatic types of Porphyria porphyrins and
related substances originate in excess amounts from the liver, 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 symptoms.  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 Porphyria.

The symptoms and treatments of the different types of Porphyrias are not
the same.  For more information on the other types of Porphyrias, choose
"Porphyria" as your search term in the Rare Disease Database or see the
"Related Disorders" section of this report.

Symptoms

The symptoms of Acute Intermittent Porphyria generally arise from effects on
the central nervous system and/or the skin.  Sometimes, the cause of the
nervous system dysfunctions are not clear, and proper diagnosis is often
delayed.  Skin manifestations can include burning, blistering and scarring of
sun-exposed areas after even minimal exposure to the sun.

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.

Many individuals who inherit the gene for Acute Intermittent Porphyria
never develop symptoms.  In those who do display symptoms, the disease may
become manifest after puberty, and more commonly does so in women than in
men.  Abdominal pain, which can be severe, is the most common symptom.  Other
symptoms may include nausea, vomiting, constipation, and pain in the back,
arms and legs.  Muscle weakness, rapid heart rate, increased blood pressure,
confusion, and hallucinations or seizures may also be present.  Sometimes the
level of salt (sodium chloride) in the blood decreases markedly during
attacks and contributes to some of these symptoms.

Because Acute Intermittent Porphyria (AIP) 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 the disease, 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.

If PBG-deaminase is deficient (approximately one-half normal) in red
blood cells, then the diagnosis of AIP is established.  However, the latter
test should not be relied upon by itself to exclude AIP in a patient, because
the result can be falsely normal or equivocal in some AIP patients.  The red
blood cell test can be extremely useful in identifying other family members
who have inherited AIP.  It should also be remembered that AIP patients can
develop other illnesses, and symptoms may not always be due to porphyria.

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

Causes

The inherited Porphyrias are either autosomal dominant or autosomal
recessive.

Acute Intermittent Porphyria is inherited as an autosomal dominant trait.
(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 may precipitate an attack of AIP include
certain drugs, chemicals, diet and sun exposure.  Depending on the type of
porphyria, these factors can greatly influence the severity of symptoms.

Because all porphyrias are uncommon, it is very unlikely that more than
one type will occur in the same family, or that someone with one type of
porphyria will go on to develop another.

Affected Population

Acute Intermittent Porphyria with symptoms is estimated to affect less than
one per one hundred thousand persons.  It occurs most frequently in people of
Scandinavian, Anglo-Saxon, or German ancestry.  It is extremely rare in
blacks.  Young or middle-aged adult women are more frequently affected than
males.

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 hereditary inborn error of metabolism which is
usually asymptomatic (latent).  It may be provoked into active disease by
administration of certain drugs, notably barbiturates, sulfonamides, and
estrogen compounds.

Congenital Erythropoietic Porphyria (CEP) is a hereditary inborn error of
metabolism that is first manifested in infancy.  Faulty conversion of PBG to
uroporphyrinogen in erythroid cells of the bone marrow and red blood cells,
leads to this type of Porphyria.  Increased porphyrins also may be formed 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 as a consequence of chronic alcoholism,
barbiturates or other chemicals, cirrhosis of the liver, or a liver (hepatic)
tumor.  It may also stem from a nutritional disorder.

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

Variegate Porphyria (VP) is a hereditary type of Porphyria due to an
inborn error of metabolism.  Precipitating or aggravating factors causing
symptoms may include exposure to barbiturates, sulfonamides, general
anesthetics, excessive amounts of ethanol, or 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 in this type of Porphyria.
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 Acute Intermittent Porphyria.  It is usually given after a
trial of glucose therapy.  Attention should be given to salt and water
balance during treatment with this drug.

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 Porphyrias are based on experience with the
patient in whom attacks have been caused by drugs, and by tests in animals.
Since many commonly used drugs have not been tested for their affects on
Porphyria, 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" section of this report).

AIP is particularly dangerous if the proper diagnosis has not been made,
and if drugs which aggravate this disorder are administered.  The prognosis
is usually good if the disease is recognized before severe nerve damage has
occurred and if treatment and preventive measures are begun.  Although
symptoms usually resolve after an attack, some patients may develop chronic
pain.  Nerve damage and associated muscle weakness can improve over a period
of months after a severe attack.  Mental symptoms may occur during attacks,
but are usually not chronic.

If the patient is taking drugs (including barbiturates, sulfonamides,
tranquilizers or sedatives, antiseizure drugs, birth control pills or
alcohol, etc.), they should be stopped under a physician's supervision.

Attacks of AIP are often precipitated by low intake of carbohydrates in
an attempt to lose weight, thus dietary counseling can be very important.
Premenstrual attacks often resolve quickly with the onset of menstruation;
hormone manipulations may prevent occurrences of such attacks.

Acute Intermittent Porphyria patients prone to attacks should eat a
normal or high carbohydrate diet and should not greatly restrict their intake
of carbohydrates and calories, even for short periods of time.  If weight
loss is desired, it is advisable to consult a physician who may then request
that a dietitian be consulted.

Pregnancy is tolerated much better in women with AIP than was formerly
believed.  Offspring have a fifty percent chance of inheriting the gene for
AIP, but the great majority of those that do remain "latent" for all or most
of their lives.  If diagnosed early, the minority that eventually have
symptoms will usually benefit from treatment.  Given these considerations,
most patients or individuals with "latent" Porphyria usually have 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 AIP
attacks.

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]

Researchers at the Mt. Sinai School of Medicine are developing a genetic
test to help identify AIP patients.  The group needs blood samples from AIP
patients to help diagnose different genetic lesions.  Anyone wishing to
participate in the research may contact:

     Dr. Cecilia Warner
     Division of Medical and Molecular Genetics
     Mt. Sinai School of Medicine
     100th St. and Fifth Ave.
     New York, NY  10029
     [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 Acute Intermittent 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 genetic information 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 Asked About
Porphyria."