CD-ROM Today 1996 January/CD-ROM Today 1996 January.iso/dp/0412/04128.txt

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$Title{Porphyria, ALA-D}
$Subject{Porphyria ALA-D Porphyria}
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Copyright (C) 1987, 1988, 1990 National Organization for Rare Disorders, Inc.

320:
Porphyria, ALA-D

** IMPORTANT **
It is possible the main title of the article (ALA-D Porphyria) may not be
the name you expected.  Please check the SYNONYMS listing to find the
alternate names and disorder subdivisions covered by this article.

Synonyms

     Porphyria

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.


ALA-D porphyria, a recently described form of acute porphyria, is
inherited as an autosomal recessive trait and seems to be extremely rare.
This form of porphyria is one of the "hepatic" porphyrias.

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

ALA-D porphyria is a recently-described form of acute porphyria whose
symptoms are very similar to those of Acute Intermittent Porphyria (AIP).
This is a deficiency of the enzyme delta-aminolevulinic acid dehydratase
(ALA-D) and there is increased excretion of ALA in the urine of patients with
this type of porphyria.

Symptoms of ALA-D 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.

Many individuals who inherit the gene for ALA-D 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 characteristics
may include nausea, vomiting, constipation, and pain in the back, arms and
legs; muscle weakness, rapid heart rate, increased blood pressure, confusion,
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 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.  If
ALA-D is deficient (approximately one-half normal) in red blood cells, then
the diagnosis of ALA-D is established.  However, the latter test should not
be relied upon by itself to exclude ALA-D in a patient, because the result
can be falsely normal or equivocal in some ALA-D patients.  The red blood
cell test can be extremely useful in identifying other family members who
have inherited ALA-D.  It should also be remembered that ALA-D patients can
develop other illnesses, and symptoms may not always be due to porphyria.

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

Causes

ALA-D porphyria is inherited as an autosomal recessive 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 recessive disorders, the condition does not appear unless a
person inherits the same defective gene from each parent.  If one receives
one normal gene and one gene for the disease, the person will be a carrier
for the disease, but usually will show no symptoms.  The risk of transmitting
the disease to the children of a couple, both of whom are carriers for a
recessive disorder, is twenty-five percent.  Fifty percent of their children
will be carriers, but healthy as described above.  Twenty-five percent of
their children will receive both normal genes, one from each parent and will
be genetically normal.)

Environmental factors that can precipitate attacks of ALA-D porphyria may
include 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

ALA-D Porphyria affects a very small segment of the world population.  Less
than one per one hundred thousand cases occurs, usually 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.

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.

Acute Intermittent Porphyria is a hereditary, usually asymptomatic
disorder (latent).  It may 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, 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.

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

ALA-D Porphyria should be treated much the same as Acute Intermittent
Porphyria (AIP).  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).

ALA-D Porphyria 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 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.

ALA-D 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
estimate an individual's normal caloric intake (this varies greatly from one
person to another).  Then it may be appropriate to prescribe a diet which is
approximately ten percent below the normal level of calories for the patient.
This usually will not cause an attack of porphyria.

Pregnancy is tolerated much better than was formerly believed.  Offspring
have a fifty percent chance of inheriting the gene for ALA-D, but the great
majority of those that will remain "latent" for all or most of their life
times.  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 indicated.

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 ALA-D 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
     England
     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."