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PORPHYRIA FACTS -
PORPHYRIA TESTING - GENERAL INFORMATION
A person who has symptoms of porphyria will have markedly abnormal
laboratory test results.
Tests must be properly selected and interpreted to confirm or exclude the
presence of porphyria.
In most cases, doctors measure the levels of delta-aminolevulinic acid and
porphobilinogen in urine when they suspect an acute porphyria, and they
measure the levels of porphyrin in the blood plasma when they suspect a
cutaneous porphyria.
Other tests, including red blood cell enzyme measurements, may be performed
when the results of one of these screening tests are abnormal.
SOURCE:
Robert Johnson M.D.
Internal Medicine
++++++++++++++++++
Diagnostic criteria for the porphyrias are poorly-defined.
SOURCE:
American Journal of Clinical Pathology,
Vol. 103, No. 6, June 1995
++++++++++++++++++
The measurements of porphyrins in urine, blood and feces are very useful for
diagnosis, especially when a patient is experiencing symptoms that suggest
porphyria.
SOURCE:
Primer on Laboratory Testing for Porphyrias
Dr. Karl E. Anderson
Porphyria Laboratory
University of Texas Medical Branch
++++++++++++++++++
Most porphyria patients can be diagnosed by obtaining a standard panel of
tests.
SOURCE:
The Porphyrias and Testing
Meszaros, Lis
Dermatology Times,
Jun96, Vol. 17 Issue 6, p14, 2p
+++++++++++++++++
Many of the tests for porphyria are highly specific and very sensitive.
SOURCE:
Primer on Laboratory Testing for Porphyrias
Dr. Karl E. Anderson
Porphyria Laboratory
University of Texas Medical Branch
Galveston TX
++++++++++++++++++
Sufficient lab testing is necessary for proper dx of porphyrias.
SOURCE:
The Porphyrias and Testing
Meszaros, Lis
Dermatology Times,
Jun96, Vol. 17 Issue 6, p14, 2p
+++++++++++++++++++
Some tests for porphyria may be abnormal in other diseases.
SOURCE:
Primer on Laboratory Testing for Porphyrias
Dr. Karl E. Anderson
Porphyria Laboratory
University of Texas Medical Branch
Galveston, TX
+++++++++++++++++++
Cost factors besides delay in diagnosis are important reasons for learning about
testing procedures and being exacting in the preparation, collection, transport
and handling of testing collections.
SOURCE:
Robert Johnson MD
Internal Medicine
++++++++++++++++++
Urine and erythrocyte porphyrins can be increased in many conditions other
than porphyrias, whereas an increased plasma porphyrin concentration is much
more specific evidence for porphyria, and increased porphyrin precursors are
much more specific evidence for the acute porphyrias.
SOURCE:
Primer on Laboratory Testing for Porphyrias
Dr. Karl E. Anderson
Porphyria Laboratory
University of Texas Medical Branch
Galveston, TX
+++++++++++++++++++
Patients who do not have any of the porphyria, but present with suggestive
symptoms and have clinically insignificant or nonspecific abnormalities in
laboratory tests for porphyrias present a dilemna in porphyria testing.
SOURCE:
Primer on Laboratory Testing for Porphyrias
Dr. Karl E. Anderson
Porphyria Laboratory
University of Texas Medical Branch
++++++++++++++++++
Preferred approach to porphyrin testing
The preferred approach in testing for porphyria is to rely on measurement of
urinary porphyrin precursors (delta-aminolevulinic acid and porphobilinogen) for
patients with neurovisceral symptoms and a fluorometric measurement of total
plasma porphyrins when one of the cutaneous porphyrias is suspected.
SOURCE:
Primer on Laboratory Testing for Porphyrias
Dr. Karl E. Anderson
Porphyria Laboratory
University of Texas Medical Branch
+++++++++++++++++++
First-Line Porphyri Tests
Heme enzyme assays should not be used as first-line tests for porphyrias when
screening patients with symptoms.
SOURCE:
Primer on Laboratory Testing for Porphyrias
Dr. Karl E. Anderson
Porphyria Laboratory
University of Texas Medical Branch
Galveston, TX
++++++++++++++++++
Porphyria testing can be undertaken when medication is stopped.
Urine specimens are sent to the laboratory for the determination of ALA, PBG
and porphyrins.
SOURCE:
The Poprhyria Center
University of Cape Town
South Africa
++++++++++++++++++
The rationale for using first line urinary testing in porphyria is that Urinary
porphobilinogen is always markedly increased
during acute attacks of acute intermittent porphyria, hereditary coproporphyria
and variegate porphyria.
SOURCE:
Primer on Laboratory Testing for Porphyrias
Dr. Karl E. Anderson
Porphyria Laboratory
University of Texas Medical Branch
+++++++++++++++++++
The use of urine and erythrocyte porphyrin measurements as first-line tests for
porphyrias is problematic.
SOURCE:
Primer on Laboratory Testing for Porphyrias
Dr. Karl E. Anderson
Porphyria Laboratory
University of Texas Medical Branch
++++++++++++++++++
Further laboratory evaluation is required if an initial screening test for porphyria
provides a positive result.
SOURCE:
Primer on Laboratory Testing for Porphyrias
Dr. Karl E. Anderson
Porphyria Laboratory
University of Texas Medical Branch
Galveston, TX
+++++++++++++++++
Second-line Porphyria Testing
After conclusive first-line and second-line testing, much more extensive (and
expensive) laboratory testing is usually justified at this point because it is
essential for management and genetic counseling to determine which type of
acute porphyria is present.
SOURCE:
Primer on Laboratory Testing for Porphyrias
Dr. Karl E. Anderson
Porphyria Laboratory
University of Texas Medical Branch
Galveston, TX
++++++++++++++++++++
Urinary, fecal and erythrocyte porphyrin measurements should usually be done
only after urinary porphyrin precursors or plasma porphyrins are found to be
increased.
SOURCE:
Primer on Laboratory Testing for Porphyrias
Dr. Karl E. Anderson
Porphyria Laboratory
University of Texas Medical Branch
Galveston, TX
+++++++++++++++++++
During acute episodes of AIP, HCP, and VP, the production urinary excretion of
delta-aminolevulinic acid (ALA) and porphobilinogen (Pbg) are increased;
therefore, quantitation of urinary ALA and Pbg during suspected acute
episodes is helpful.
SOURCE:
Porphyria Resources
United Medical Services
1996
+++++++++++++++++++
After first-line and second-line tests more specific tests are judtified in
symptomatic persons.
This may include measurement of plasma, urinary and fecal porphyrins and
selected heme biosynthetic pathway enzymes.
SOURCE:
Primer on Laboratory Testing for Porphyrias
Dr. Karl E. Anderson
Porphyria Laboratory
University of Texas Medical Branch
Galveston, TX
++++++++++++++++++++
Fecal testing & diet
Fecal porphyrin determinations may be confounded by variations
in fecal flow and by substances in the diet.
SOURCE:
Primer on Laboratory Testing for Porphyrias
Dr. Karl E. Anderson
Porphyria Laboratory
University of Texas Medical Branch
Galveston, TX
+++++++++++++++++++
Testing during remission
It does become more difficult to "rule out porphyria" if testing is delayed until
after there is resolution of symptoms.
SOURCE:
Primer on Laboratory Testing for Porphyrias
Dr. Karl E. Anderson
Porphyria Laboratory
University of Texas Medical Branch
Galveston, TX
++++++++++++++++++
In the mutation-screened population, urinary PBG analysis identified only 85% of
81 AIP patients studied during remission.
It was increased </=2-fold in 29% of healthy relatives.
SOURCE:
Molecular and biochemical studies
of acute intermittent porphyria in 196 patients and their families.
Kauppinen R, Von Und Zu Fraunberg M.
Department of Medicine
Division of Endocrinology
University Hospital of Helsinki
Helsinki, Finland.
Clinical Chemistry
2002 Nov;48(11):1891-900
++++++++++++++++
Porphyrias seldom become completely latent (such that all levels of porphyrins
and porphyrin precursors become normal) within a short period of time.
SOURCE:
Primer on Laboratory Testing for Porphyrias
Dr. Karl E. Anderson
Porphyria Laboratory
University of Texas Medical Branch
Galveston, TX
++++++++++++++++++++
Urine samples also are often collected when a patient is not experiencing
an acute porphyria attack and porphyrin levels have dropped to the normal
range.
SOURCE:
American Journal of Clinical Pathology,
Vol. 103, No. 6, June 1995.
+++++++++++++++++++
AIP testing is usually reliable during the acute phase of the illness as
concentrations are generally lower between attacks and can be withint the
normal reference range.
SOURCE:
American Journal of Clinical Pathology,
Vol. 103, No. 6, June 1995.
+++++++++++++++++++
DNA Testing
DNA testing is ideal for detecting carriers of a known mutation in a particular
enzyme, but requires that the mutation first be fully characterized in the
propositus.
SOURCE:
Primer on Laboratory Testing for Porphyrias
Dr. Karl E. Anderson
Porphyria Laboratory
University of Texas Medical Branch
Galveston, TX
+++++++++++++++++++
Measurement of the deficient enzyme, or DNA testing, may be useful when
asymptomatic relatives are being screened for porphyria.
SOURCE:
Primer on Laboratory Testing for Porphyrias
Dr. Karl E. Anderson
Porphyria Laboratory
University of Texas Medical Branch
Galveston, TX
+++++++++++++++
Heme Assay Testing
Heme enzyme assays are useful for family studies, when it is established that an
index case has a particular enzyme deficiency .
SOURCE:
Primer on Laboratory Testing for Porphyrias
Dr. Karl E. Anderson
Porphyria Laboratory
University of Texas Medical Branch
Galveston, TX
++++++++++++++
Assays for heme biosynthetic pathway enzymes in erythrocytes have become
widely available through commercial laboratories.
SOURCE:
Primer on Laboratory Testing for Porphyrias
Dr. Karl E. Anderson
Porphyria Laboratory
University of Texas Medical Branch
Galveston, TX
+++++++++++++++++++
Plasma Porphyrins
In contrast to plasma porphyrins, no other tests detects all cutaneous
porphyrias.
SOURCE:
Primer on Laboratory Testing for Porphyrias
Dr. Karl E. Anderson
Porphyria Laboratory
University of Texas Medical Branch
Galveston, TX
+++++++++++++++
Misdiagnosis
Overuse and overinterpretation of minor abnormalities in results of second-line
tests including erythrocyte porphobilinogen
deaminase, other enzyme assays, and fractionation of urinary and fecal
porphyrins, account for many incorrect diagnoses of porphyria.
SOURCE:
Primer on Laboratory Testing for Porphyrias
Dr. Karl E. Anderson
Porphyria Laboratory
University of Texas Medical Branch
Galveston, TX
++++++++++++++++
It is less widely appreciated that incorrect diagnoses of porphyria are common in
patients with symptoms due to other diseases.
SOURCE:
Primer on Laboratory Testing for Porphyrias
Dr. Karl E. Anderson
Porphyria Laboratory
University of Texas Medical Branch
Galveston, TX
++++++++++++++++++
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.
SOURCE:
Primer on Laboratory Testing for Porphyrias
Dr. Karl E. Anderson
Porphyria Laboratory
University of Texas Medical Branch
Galveston, TX
++++++++++++++++++++
Re-testing
Why is re-testing necessary of a person with a diagnosis?
In patients with a past history of porphyria it is important to review the laboratory
data that were the basis for the original diagnosis.
SOURCE:
Primer on Laboratory Testing for Porphyrias
Dr. Karl E. Anderson
Porphyria Laboratory
University of Texas Medical Branch
Galveston, TX
++++++++++++++++++
One can not ignore the importance of sufficient laboratory testing for the proper
diagnosis of patients with various forms of porphyrias.
SOURCE:
The Porphyrias and Testing
Meszaros, Lis
Dermatology Times,
Jun96, Vol. 17 Issue 6, p14, 2p
+++++++++++++++++++
It may be necessary to retest either the propositus or another family member
with confirmed porphyria before undertaking screening of family members.
SOURCE:
Primer on Laboratory Testing for Porphyrias
Dr. Karl E. Anderson
Porphyria Laboratory
University of Texas Medical Branch
Galveston, TX
+++++++++++++++++++
Moreover, hemolysis of a blood sample invalidates a plasma porphyrin
determination because normal erythrocytes contain much larger amounts
of porphyrin (in the form of Zn protoporphyrin) than does normal plasma.
SOURCE:
Primer on Laboratory Testing for Porphyrias
Dr. Karl E. Anderson
Porphyria Laboratory
University of Texas Medical Branch
++++++++++++++++++++
Key Issues in Testing
If porphyria is suspected sodium carbonate rather than an acid should be used
because it will be important to measure porphobilinogen and possibly porphyrins
as well as delta-aminolevulinic acid.
SOURCE:
Primer on Laboratory Testing for Porphyrias
Dr. Karl E. Anderson
Porphyria Laboratory
University of Texas Medical Branch
++++++++++++++++++
Acid conditions enhance
degradation of porphobilinogen.
SOURCE:
Primer on Laboratory Testing for Porphyrias
Dr. Karl E. Anderson
Porphyria Laboratory
University of Texas Medical Branch
+++++++++++++++++
Urine samples are not kept refrigerated.
Such collections should be keep refrigerated at all times
between 36 and 40 degrees F.
SOURCE:
American Journal of Clinical Pathology,
Vol. 103, No. 6, June 1995.
++++++++++++++++++++
After initial evaluation of urine collections the diagnosis should ideally be
confirmed by additional testing of blood and fecal specimens.
Most attacks of the acute porphyrias are associated with a uro/hepta ratio
>4, and can be confirmed by an elevated urine porphobilinogen concentration.
SOURCE:
K. Nutall M.D.
Annals of Clinical Laboratory Science
2001 Jul;31(3):259-64
+++++++++++
Assaying Porphyrin Tests
Difficulties with porphyrin assays in clinical practice include the fact
that ranges for a particular porphyria and normals may overlap.
SOURCE:
Primer on Laboratory Testing for Porphyrias
Dr. Karl E. Anderson
Porphyria Laboratory
University of Texas Medical Branch
Galveston, TX
++++++++++++++++++
Because of all of the variables in testing results, experience is often important
in interpreting tests for porphyrias.
SOURCE:
Primer on Laboratory Testing for Porphyrias
Dr. Karl E. Anderson
Porphyria Laboratory
University of Texas Medical Branch
Galveston TX
++++++++++++++++++++
Window Sill Test
One simple test for porphyria is to expose a cup of urine to sunlight for the better
part of a day.
If the urine becomes wine colored or purple, porphyria is probable.
However, lack of color changes will NOT indicate that porphyria is unlikely.
SOURCE:
Porphyria
Greek for "Purple Urine"
Orthomolecular Medicine
+++++++++++++
Testing for Specific Types of Porphyria
PNG-D deficiency in AIP is associated with a marked increase of hepatic
delta-aminolevulinic acid synthetase, the first and rate controlling enzyme of the
pathway.
The measurement of uroporphyrinogen I synthetase in erythrocytes now
provides an enzyme diagnostic test for the disease.
SOURCE:
Acute intermittent porphyria:
clinical and selected research aspects.
Tschudy DP, Valsamis M, Magnussen CR.
Annals of Internal Medicine
1975 Dec;
83(6):851-64.
++++++++++++++++++++++
People with (CEP) congenital erythropoietic porphyria have significantly
increased levels of two specific porphyrins--uroporphyrin and coproporphyrin--in
their urine and feces.
Urine and stool tests can diagnose the condition by measuring the levels of
these compounds.
Another test measures the activity of uroporphyrinogen III synthase in red blood
cells.
The enzyme's activity is reduced to less than 15 percent of normal in people with
the disorder.
SOURCE:
Lister Hill National Center for
Biomedical Communications
National Institutes of Health
Department of Health & Human Services
++++++++++++++++++++++
The sensitivity of urinary and fecal coproporphyrin analysis of VP patients
studied shows positive results of 48% and 52%, respectively.
SOURCE:
Diagnosis of variegate porphyria--hard to get?
Fraunberg M, Kauppinen R.
Department of Medicine
University Hospital of Helsinki, Finland.
Scandinavian Journal of
Clinical Laboratory Investigation
2000 Nov;60(7):605-10
+++++++++++++++++++++
The most reliable clinical assay for diagnosing patients with AIP Type I,
whether symptomatic or latent, is the assay for erythrocyte
PBG deaminase.
SOURCE:
American Journal of Clinical Pathology,
Vol. 103, No. 6, June 1995
+++++++++++++++++++++
To further complicate the diagnosis of AIP, a subgroup of AIP patients
have normal PBG deaminae activity in erythrocytes, although the activity
of the hepatic enzyme is decreased.
SOURCE:
American Journal of Clinical Pathology,
Vol. 103, No. 6, June 1995.
+++++++++++++++++++++
The activity of porphobilinogen deaminase was determined in 25 patients with
acute intermittent porphyria during and after fully developed attacks of porphyria.
It was found that in most cases (in 20 of 25) it was higher than 24.3 nmoles/ml
erythrocytes/hour, a value considered as characteristic for acute intermittent
porphyria, and that it decreased during convalescence and remission.
In a proportion of these cases the decrease in the activity of the enzyme was
parallelled by decreasing urinary excretion of porphobilinogen.
A normal activity of porphobilinogen deaminase during an attack of porphyria
can be a source of error in the differential diagnosis of porphyria.
SOURCE:
"Increased activity of porphobilinogen deaminase in erythrocytes during attacks
of acute intermittent porphyria."
Kostrzewska, E. and A. Gregor
Annals of Clinical Research
1986; 18(4): 195-8.
++++++++++++++++++++++
Elevated amounts of porphobilinogen and alpha-aminolevulinic acid in urine and
in plasma are confirmatory laboratory testsfor acute intermittent porphyria (AIP).
SOURCE:
Treatment of Hypertension in a
Patient With Acute Intermittent Porphyria?
Bruce Gardner, MD
Associate Clinical Professor of Family Medicine
University of Washington, Seattle
Attending Physician, Family Medicine
Swedish Hospital and Medical Center, Seattle
+++++++++++++++++++
Normal plasma porphyrin levels exclude porphyria as a cause of cutaneous
symptoms if the measurement is carried out by a simple and direct fluorometric
method..
SOURCE:
Primer on Laboratory Testing for Porphyrias
Dr. Karl E. Anderson
Porphyria Laboratory
University of Texas Medical Branch
++++++++++++++++++++
When cutaneous symptoms are present, the most useful first-line test for
porphyria is the measurement of total plasma porphyrins, which are always
increased in patients with active skin lesions.
SOURCE:
Primer on Laboratory Testing for Porphyrias
Dr. Karl E. Anderson
Porphyria Laboratory
University of Texas Medical Branch
+++++++++++++++++++
Porphobilinogen is also increased in serum in the acute porphyrias, although the
concentrations are lower than in urine.
SOURCE:
Primer on Laboratory Testing for Porphyrias
Dr. Karl E. Anderson
Porphyria Laboratory
University of Texas Medical Branch
+++++++++++++++++++
Urinary Testing Kits
A commercial semi-quantitative kit (Trace) for urinary porphobilinogen (PBG) in
which urine is pre-treated with ion-exchange resin and the colour of the
Ehrlich-PBG adduct matched against a set of surrogate standards has been
compared with qualitative screening methods (Watson-Schwartz) which has
been in common use for many years.
Twenty samples in which PBG had been quantitated were blindly tested byboth
methods in each of 13 typical user laboratories.
For urine samples with raised PBG, 123 out of 129 results were positive when
tested with the Trace kit.
Using qualitative tests routinely in use in the various laboratories only 45 out of
119 results were unequivocally positive.
Sixteen out of 91 results for pigmented urine samples with normal PBG were
reported as positive using qualitative screening tests,but only one using the
Trace kit."
Therefore, the Trace method is far more sensitive and specific than the
qualitative screening tests.
It is recommended that Watson-Schwartz-type screening tests should be
abandoned and, ideally, all urine samples analysed by quantitative methods.
However, the Trace method is a convenient alternative which is
adequate for the INITIAL screening of symptomatic patients.
SOURCE:
Annals Clinical Biochemistry 1998 Nov;35 (Pt 6):726-32
"Identification of acute porphyria: evaluation of a commercial screening test for
urinary porphobilinogen."
Authors: Deacon AC MD, and Peters TJ MD
Department of Clinical Biochemistry,
King's College Hospital,
Denmark Hill,
London, UK.
+++++++++++++++++
Testing of Latent Carriers
Even in porphyrias that are inherited in an autosomal dominant pattern,
there may be no such increases in many family members who carry the
abnormal gene.
SOURCE:
Primer on Laboratory Testing for Porphyrias
Dr. Karl E. Anderson
Porphyria Laboratory
University of Texas Medical Branch
Galveston, TX
+++++++++++++++++++
***See also:
Testing of Children
SOME QUESTIONS TO ASK ABOUT TESTS AND PROCEDURES
1. How will this test aid in the diagnosis or therapy of my illness?
2. Will I need to be hospitalized?
3. Will other tests need to be done?
4. Will I need other tests in the future, or will I need this test repeated?
5. Are there simpler or less risky ways to evaluate my symptoms?
6. What if no diagnosis is made? Will you then simply observe me to see if
the symptoms go away, or will you possibly have to go as far as exploratory
surgery?
7. Do I have any particular risk factors for any of the tests?
8. Will my insurance cover the costs of tests done either inside or outside
of the hospital?
9. Please explain to me exactly what you are going to do during this test
before you start.
10. How long will it take?
11. Can I expect any unusual feelings, pain, or sensations?
12. Will I need someone to drive me home after the procedure is over, or
will it be safe to drive myself?
13. What are the risks of this test, and how often do they happen? Am I at
particular risk?
14. Are there special instructions to follow before or after this test?
15. Will I need to be seen after the test is done?
16. Will you call me with the test results, and can I get a copy of them for
my personal records?
17. How will I know if a complication is occurring?
18. What should I do if I experience a complication?
19. Are there any side effects I should be concerned about?
.
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