Acute intermittent porphyria is a subtype of porphria, a rare and
very interesting genetic disease. AIP occurs in 1.5 persons out of
100,000 people, with an increased incidence in England, Ireland, and
?Acute intermittent porphyria is inherited in an autosomal dominant
pattern, which means one copy of the altered gene is sufficient to
decrease enzyme activity and cause symptoms.?
?Acute intermittent porphyria - Acute intermittent porphyria (AIP)
is also known as Swedish porphyria, pyrroloporphyria, and intermittent
acute porphyria. AIP is inherited as an autosomal dominant trait,
which means only one copy of the defective gene needs to be present
for the disorder to occur. However, simply inheriting this gene does
not necessarily mean that a person will develop the disease.
Approximately 5-10 per 100,000 persons in the United States carry the
gene, but only10% of them ever develop AIP symptoms.?
?Treatment for acute intermittent porphyria, hereditary
coproporphyria, and variegate porphyria follows the same basic regime.
A person who has been diagnosed with one of these porphyrias can
prevent most attacks by avoiding precipitating factors, such as
certain drugs that have been identified as triggers for acute
porphyria attacks. Individuals must maintain adequate nutrition,
particularly in respect to carbohydrates. In some cases, an attack can
be stopped by increasing carbohydrate consumption or by receiving
If an attack occurs, medical attention is needed. Pain is usually
severe, and narcotic analgesics are the best option for relief.
Phenothiazines can be used to counter nausea, vomiting, and anxiety,
and chloral hydrate or diazepam is useful for sedation or to induce
sleep. An intravenously administered drug called hematin may be used
to curtail an attack. It seems to work by signaling the heme
biosynthesis pathway to slow production of precursors.?
?The porphyrias are inherited conditions, and the genes for all
enzymes in the heme pathway have been identified. Some forms of
porphyria result from inheriting an abnormal gene from one parent
(autosomal dominant). Other forms are from inheriting an abnormal gene
from each parent (autosomal recessive). The risk that individuals in
an affected family will have the disease or transmit it to their
children is quite different depending on the type.?
?The predominant problem appears to be neurologic damage that leads
to peripheral and autonomic neuropathies and psychiatric
Although patients with acute attacks always have elevations of
porphobilinogen and ALA, how this leads to the symptomatic disease is
still unclear because most patients with the genetic defect have
excessive porphyrin secretion but no symptoms.?
?The classic inducers of porphyria are chemicals or situations that
boost heme synthesis. This includes fasting and many medications.
Although very large lists of "safe" and "unsafe" drugs exist, many of
these are based on anecdotes or laboratory evidence and do not meet
strict criteria. In general, drugs that lead to increased activity of
the hepatic P450 system, such as phenobarbital, sulfonamides,
estrogens, and alcohol, are associated with porphyria.?
?Fasting for several days also can trigger an attack. However, many
attacks occur without any obvious provocation.?
?Most people with a deficiency of porphobilinogen deaminase never
develop symptoms. In some people, however, certain factors?drugs,
hormones, or diet?can precipitate symptoms, producing an attack. Many
drugs (including barbiturates, anticonvulsants, and sulfonamide
antibiotics) can bring on an attack. Hormones, such as progesterone
and related steroids, can precipitate symptoms, as can low-calorie and
low-carbohydrate diets, large amounts of alcohol, or smoking. Stress
resulting from an infection, another illness, surgery, or a
psychologic upset is also sometimes implicated. Usually a combination
of factors is involved. Sometimes the factors that cause an attack
cannot be identified.?
?There are seven main types of porphyria (fig 1), which are broadly
classified according to clinical features into neuropsychiatric,
dermatological, and mixed forms. Acute intermittent porphyria and
plumboporphyria are predominantly neuropsychiatric; congenital
erythropoietic porphyria, porphyria cutanea tarda, and erythropoietic
protoporphyria have predominantly cutaneous manifestations; and
hereditary coproporphyria and variegate porphyria are classified as
mixed as they may have both cutaneous and neuropsychiatric features.
The prevalence of porphyria varies widely from country to country and
also depends on the type of porphyria. Overall prevalence of overt
cases in the United Kingdom is about 1 in 25 000 population for
porphyria cutanea tarda and less than 1 in one million for congenital
erythropoietic porphyria.1 Plumboporphyria has not been reported in
??not all symptoms in porphyric patients are due to porphyria
porphyric patients are not immune to other conditions.?
?Routine laboratory screening tests may be unreliable,14 but a
recently introduced screening kit seems promising.15 A clue to the
diagnosis is that the urine is often dark on standing owing to
polymerisation of porphobilinogen to porphyrins and other pigments.
Between attacks, however, concentrations of urinary porphobilinogen
and particularly aminolaevulinic acid are often normal. Plasma
fluorescence is usually increased in variegate porphyria and is
valuable both diagnostically and for family studies.?
?The isolation and characterization of the gene for PBG deaminase
has brought molecular techniques for diagnosing the disease within
reach. Over 60 mutations causing acute intermittent porphyria have
been found, most of which are confined to one or several families.
Because no single mutation accounts for more than a fraction of cases,
screening techniques for locating and identifying unknown mutations
are very important. Once a mutation has been characterized, testing of
family members is straightforward, and gene carriers can be identified
or excluded with greater accuracy than is possible with conventional
?The best time to be tested for porphyria is at the earliest
opportunity. In practice, this means that families should be offered
screening for acute porphyria as soon as possible after a relative has
been found to have the condition. When one or other parent is already
known to have an acute porphyria, their children should be tested as
soon as practicable. It is worth enquiring about this during pregnancy
as your doctor will then be able to find out when your baby should be
tested. In some cases, it is now possible to test baby at birth but it
may be necessary to wait until your child is one year old or,
occasionally, even older.
There are two main advantages of early diagnosis. First, those who are
found to have inherited one of the acute porphyrias can be advised
about how to reduce the risk of an acute attack. Second, if an acute
attack does develop, your doctor will be able to make the diagnosis
and start special treatment early. The symptoms of an attack of acute
porphyria are not always easy to recognise and, if the condition is
not already diagnosed, there is a risk that your doctor will use drugs
that may make the attack worse or may even think that an operation is
?For relatives who have not had an acute attack, and especially for
children, urine testing is usually unhelpful. For these people,
special tests on blood, and sometimes urine or faeces as well, need to
be carried out in a specialist reference laboratory (more about
porphyria specialist centres). For some families, it is now becoming
possible to use DNA tests to detect the gene mutation that causes
porphyria. DNA tests are more accurate than other methods but are
complicated and are not yet available for all families. Your doctor
should be able to arrange specialist testing for you. If you live a
long way from a specialist porphyria laboratory, the samples can
easily be sent by post following specific advice.?
?One should never accept a diagnosis of porphyria based on
clinical symptoms alone. Skin symptoms suggestive of photosensitivity
are indeed sufficient reason to have a patient tested for porphyria,
as are are symptoms suggestive of the acute attack. Bear in mind
however that appropriate diagnostic laboratory tests must be regarded
as more sensitive and specific than the clinical history alone. In
particular, to have any relevance, the skin symptoms and possible
acute symptoms must be consistent with these diagnoses.?
?A point often not appreciated by both patients and doctors is that an
accurate set of diagnostic results will provide more information than
merely confirming that porphyria is present. In order to manage the
patient appropriately, we require the following information from our
? a definitive diagnosis of the type of porphyria.
? an estimation of the biochemical activity of the porphyria. (In
general there is a relationship between the the degree of elevation of
urine ALA, PBG and porphyrins and the likelihood that acute symptoms
are due to porphyria.)
? identification of the mutation responsible for the porphyria in the
patient (which is of great value in subsequent screening of the
Here is a chart of the most common symptoms
??the diagnosis of AIP and other types of porphyria is sometimes
made incorrectly in patients who do not have porphyria at all,
particularly if laboratory tests are improperly done or
misinterpreted. The finding of increased levels of
delta-aminolevulinic acid (ALA) and porphobilinogen (PBG) in urine
establishes that one of the acute porphyrias is present. If PBGD is
deficient in normal red blood cells then the diagnosis of AIP is
established. However, measuring PBGD in red blood cells should not be
relied upon by itself to exclude AIP in a sick patient, because the
enzyme is not deficient in red blood cells of all AIP patients.?
?However, in some AIP families, PBGD is normal in red blood cells and
is deficient only in the liver and other tissues. Falsely low values
sometimes occur due to problems with collecting and transporting the
As a health care professional myself, I can tell you that handling
of specimens is a huge problem. Specimens MUST be processed correctly
and kept from light at all times. A delay in transport, specimen
collection and labeling, and delay in testing can alter results. If
possible, try to collect your samples (except 24 hour samples, of
course) at the performing lab to avoid transport delays. Make sure the
samples are well protected from light. Wrap containers with an old
rag, then cover with foil, so no light enters the container. Ask the
technician or nurse collecting your samples to cover the tubes
immediately after drawing them.
?Porphyrin tests are assays that are used to help diagnose, and
monitor a group of disorders called porphyrias. Most porphyrin tests
detect and measure the by-products of heme synthesis. Heme is a part
of hemoglobin (the protein inside red blood cells that allows them to
transport oxygen) and a number of other proteins. The synthesis of
heme is a step-by-step process that requires the sequential action of
eight different enzymes. If there is a deficiency in one of these
enzymes, a bottleneck forms and precursors build up in the body?s
fluids and tissues and are excreted in urine and feces. Which
precursors build up depends on where the bottleneck is.?
Clinical laboratories measure porphyrins and their precursors in
urine, blood, and feces. These tests are listed below:
? Delta-aminolevulinic acid (ALA) in urine
? Porphobilinogen (PBG) in urine
? Porphyrins in urine, feces, or blood
? Zinc protoporphyrin (or free erythrocyte protoporphyrin) in red blood cells
?It is less widely appreciated that incorrect diagnoses of
porphyria are common in patients with symptoms due to other diseases.
Therefore, in patients with a past history of porphyria, it is
important to review the laboratory data that were the basis for the
original diagnosis. Further testing may be necessary if the diagnosis
was not adequately documented.
Incorrect diagnoses of porphyria can occur in patients having minimal
abnormalities in laboratory tests, such as small elevations in urinary
porphyrins or porphyrin precursors that in fact have little or no
diagnostic significance. Incorrect diagnoses are less likely if
reliance is placed on a few first-line tests in most clinical
situations, as described above.?
This testing flow chart will be useful to you:
?Laboratory tests performed on samples of urine show increased
levels of two heme precursors (delta-aminolevulinic acid and
porphobilinogen). Levels of these precursors are very high during
attacks and remain high in people who have repeated attacks. The
precursors can form porphyrins, which are reddish in color, and other
substances that are brownish. These turn the urine dark, especially
after exposure to light.?
?Attacks of acute intermittent porphyria can be prevented by
maintaining good nutrition and avoiding the drugs that can provoke
them. Crash diets to lose weight rapidly should be avoided. Heme can
be given to prevent attacks. Premenstrual attacks in women can be
prevented with one of the gonadotropin-releasing hormone agonists used
to treat endometriosis (see Endometriosis), although this treatment is
??The fundamental step in diagnosing acute intermittent porphyria
(AIP) is to demonstrate increased urinary porphobilinogen secretion.
If a patient has no increased secretion of porphobilinogen, acute
porphyria is eliminated as a cause of the neurovisceral symptoms.
o A common error is the failure to order urine porphyrins.
Porphobilinogen, a porphyrin precursor, usually is not included in a
urine porphyrin screen and must be ordered specially.
o AIP patients have elevated porphobilinogen between attacks.
oI n some patients with a remote (years) history of attacks,
porphobilinogen can return to the reference range.
?Other nonspecific signs in an attack of AIP include hyponatremia,
(Low blood sodium) syndrome of inappropriate secretion of antidiuretic
hormone (SIADH), and mild leukocytosis (increased white blood cell
?Although a defective enzyme causes AIP, measuring the activity of
porphobilinogen deaminase is of little value.
o Approximately 10% of AIP patients will have normal activity because
a different form of the enzyme is expressed in the hematopoietic
o The vast majority of patients with the defective enzyme do not have
any symptoms of the disease.
?The treatment goal for acute attacks of porphyria is to decrease heme
synthesis and reduce the production of porphyrin precursors.
o High doses of glucose (400 g/d) can inhibit heme synthesis and are
useful for treatment of mild attacks.
o People experiencing severe attacks, especially those with severe
neurologic symptoms, should be treated with hematin in a dose of 4
mg/kg/d for 4 days.
?Pain control is best achieved with narcotics. Laxatives and stool
softeners should be administered with the narcotics to avert
exacerbating existing constipation.
?Treat seizures with Neurontin. Most classic antiseizure medicines can
lead to acute porphyria attacks.
?The patient should receive a high-carbohydrate diet during the
attack. If the patient is unable to eat, intravenous glucose should be
?Between attacks, eating a balanced diet is more important than eating
one rich in glucose.
?Acute Attack Porphyria: Test for urine porphobilinogen. Urine PBG
is the single most important test if an acute porphyria is suspected.
During an acute attack, urine PBG is markedly elevated. A random urine
sample collected during a symptomatic episode is an excellent specimen
for the evaluation of an acute porphyria. Alternatively, a 24-hour
urine specimen may be collected.
Aminolevulinic acid (ALA) is also typically elevated during an acute attack.?
?It is difficult to diagnosis latent acute porphyria because
concentrations of PBG typically normalize between attacks and more
than 90 percent of individuals who carry the gene defect never suffer
from an acute attack. Enzyme concentrations can, in theory, identify
individuals at risk. For example, in individuals predisposed to acute
intermittent porphyria, the concentration of the enzyme PBG deaminase
is typically half that seen in unaffected individuals. (See also:
Porphobilinogen (PBG) Deaminase, Erythrocyte.) Technical difficulties
limit the usefulness of enzyme assays, however, and gene-based assays
may prove to be more reliable.?
Please see this cached site for the normal ranges of urine porphobilinogen.
Urine porphyrin and precursor analysis
?This may confirm a diagnosis of acute intermittent porphyria or
porphyria cutanea tarda, and is the most appropriate way to assess the
biochemical activity of variegate porphyria.?
?A common problem is the patient who has had an incomplete sets of
tests performed. Typically this comprises a DNA test for the common
South African mutation without appropriate biochemical urine and
plasma porphyrin analysis. Such a test will not detect forms of
porphyria other than R59W-positive VP, and provides no information on
?What investigation should be done if Porphyria is suspected?
? biochemistry - hyponatraemia, hypomagnesaemia and hypovolaemia may
occur during acute attacks
? definitive test is porphobilinogen deaminase in erythrocytes which
is decreased by 50%
? urine - usually normal colouration when fresh but becomes brown, red
or black on standing; marked increase in porphobilinogen (PBG);
slightly elevated coproporphyrin and uroporphyrin
? stool - coproporphyrin and protoporphyrin normal
? liver function tests - sulfobromophthalein retention
? increased serum cholesterol, serum iron and T4
? abnormal glucose tolerance
What is the Ehrlich Aldehyde Test ?
Ehrlich's aldehyde test is used to confirm a diagnosis of acute
intermittent porphyria. Ehlich's aldehyde reagent consists of
p-dimethyl amino benzaldehyde in acid solution. Equal volumes of urine
and Ehrlich's reagent are mixed. If a pink colour is formed this
indicates a raised urinary concentration of either porphobilinogen or
urobilinogen. In cases of raised porphobilinogen, as in acute
intermittent porphyria, the pink precipitate is observed to be
insoluble in chloroform.?
This site is now closed, so if you find the information useful, you
may wish to copy the pages. It is unknown how long this page will be
?A genetic counselor can review your family history and risks for
this disorder in you and your offspring and discuss appropriate
testing that is available for you.
Although the genetic mutation cannot be corrected, attacks can be
anticipated, prevented, or controlled. Steps to avoid porphyria
attacks and complications include the following:
?Avoid drugs and other triggers
?Protect skin from injury or infection
From the University of Cape Town, I found this great glossary of
porphyria terms form you!
Porphyria Education materials from the Porpria Foundation
For further AIP education, consider these books:
I hope you found this information useful. If anything is unclear,
please request an Answer Clarification, and allow me to respond,
before your rate this answer!
I wish you the best!
Ehrlich's aldehyde test + porphyria
Porphobilinogen + urobilinogen
Acute Intermittent Porphyria + testing algorithm
AIP + glucose
AIP + testing flow chart
Coping with AIP