TESTING FOR PORPHYRIA
|Laboratory Testing & The
Today there is increasing need for testing for porphyrin disorders:
The primary porphyrin disorders, which are considered the
inherited porphyrias, fall into three clinical categories:
 The acute attack forms of porphyria are usually
characterized by neurological and psychiatric manifestations.
 Those with cutaneous photosensitivity.
 Those with both neurological symptoms and photosensitivity.
When testing is begun to determine if a patient has a definitive
diagnosis of porphyria tsting is usually begun with the basic 24 urine porphyrin test. Based upon the results of that test a variety of other porphyrin tests will follow.
In the acute hepatic porphyrias which include: AIP [acute
intermittent porphyria; VP [variegate porphyria]; and HCP [hereditary
coproporphyria] the test for urine porphobilinogen (PBG). Urine PBG is the single most important test when considering an acute porphyrias.
During an acute attack, urine PBG is markedly elevated.
A random urine collected during a symptomatic episode is an
excellent specimen for the evaluation of an acute porphyria.
Most often a 24-hr urine specimen may be collected.
Delta-Aminolevulinic acid (ALA) is also typically elevated
during an acute attack.
In the acute hepatic porphyrias, an acute porphyria may present
with symptoms of abdominal pain, limb or chest pain, nausea, paresthesias,
weakness, confused thoughts, depression, hallucinations, and psychosis.
Such acute attacks are usually accompanied by signs which
often include hypertension [high blood pressure] and tachycardia.[a racing
heart beat or fast pulse].
Constipation or diarrhea may occur during acute attacks. Nausea can be accompanied by vomiting and may be controlled safety with the use of compazine or thorazine. Less common symptoms include fever, profused weating, convulsions [tremors or seizures or/and ANS] , and respiratory paralysis.
Acute attacks generally have a rapid onset of hours to days, but
characterization of a typical episode is impossible. An attack may last
several days to several weeks. Please note that no two people will react in
the same way to an acute attack, and the same patient will find that no two
attacks will have the same reactions.
An acute attack is often precipitated by some event or drug
exposure. Known pharmaceuticals associated with attacks include ethanol, barbiturates, and anticonvulsants.
An attack may be precipitated by dietary restriction.such as
experienced in crash diets, or the avoidance of carbohydrates.
In women many attacks are influenced by hormonal status, with
the disease typically becoming manifest after puberty. Acute attacks which
are more common in women, may occur in association with menses usually a week prior to the oinset. In some women the acute attacks may cease with menopause. Some women have clinically been charted with more aggressive attacks. It is important for women to remember that estrogen replacement should be avoided as it has been indicated as a trigger for acute attacks.
Several acute porphyrias exist, including acute intermittent
porphyria. AIP as it is called, is the most common form of porphyria. VP, also known as variegate porphyria, and HCP known as hereditary coproporphyria are very similar to AIP and are treated in the same way.
Both the VP and the HCP are also associated with cutaneous
photosensitivity in about 30% of the cases.
The neurologic and psychiatric symptoms of VP and HCP are
essentially identical to those found in AIP, and thus most information on porphyrias is usually discussed in relation to AIP, which only the specific testing information in additon.
Acute attacks are invariably associated with elevated
concentrations of PBG and ALA. Rare ALA synthase deficiency porphyria is associated with elevated ALA . PBG is usually not associated with this..
Often porphyria patients complain about the testing and retesting
it takes to have a definitive diagnosis. It is very hard to make accurate assays and this is especially true to determine whether a type is VP or HCP.
It is also difficult to diagnosis an acute porphyria between
attacks for a variety of reasons.
The foremost reason is that more than 90% of individuals who
carry the gene defect never suffer from an acute attack.
The second reason is that abnormal concentrations of PBG
typically normalize between attacks. Enzyme concentrations can, in theory,
identify individuals at risk. For example, in individuals predisposed to acute intermittent porphyria, the enzyme PBG deaminase is typically half the levels seen in normal individuals.
Many technical difficulties limit the practical usefulness of
such enzyme assays, however, and gene-based assays will probably prove to be more reliable. Gene-based testing is currently available through Mt. Sinai for acute intermittent porphyria, but not for the other acute porphyrias. The HCP assay has been revised at the Mayo Labs so that a clearly distinction can be made between the VP and the HCP.
Cutaneous photosensitivity due to a porphyrin disorder is
associated with elevated porphyrin concentrations. This is opposed to
elevated ALA and PBG. The most useful diagnostic specimens include urine and serum (or plasma).
Bile and feces may also be used, although fecal porphyrins
suffer from extensive bacterial degradation, and bile specimens are
difficult to collect.
Urine is the best specimen with which to diagnose porphyria
cutanea tarda (PCT). PCT is the most common photosensitive-type porphyria presenting in adults. PCT typically present with bullous vesicles on sun-exposed skin, although the association with sun exposure in often not recognized.
Serum and plasma are excellent specimens with which to evaluate
Total serum porphyrins are diagnostic for erythropoietic protoporphyria,
[EPP]which often presents in childhood with relatively mild photosensitivity.
Total serum porphyrins are also markedly abnormal in a variety
of other porhyrin disorders, including PCT (although fractionated urine
porphyrins are more diagnostic).
Serum porphyrins are often abnormaL in varegate porphyria,
although bile provides the most diagnostic specimen.
A definitive diagnosis of any one of eight main porphyrias and their
subsets is based upon the assay of any or all of the various porphyrin tests.
The initial and basic test when a physician suspects porphyria is
to order the "Urine Porphyrin" test. [Code #: 0080460] Such a test uses the high performance iquid chromatography method (HPLC).
Urine porphyrins are very basic for the evaluation of cutaneous
photosensitivity . The results of the test will help to exclude porphyria
cutanea tarda (PCT).
When physicians are undertaking an evaluation of neurologic and/or
the psychiatric symptoms associated with acute forms of porphyrias require urine porphobilinogen (PBG) testing.
When an acute neurological porphyria is suspected, a determination
of urinary porphobilinogen (PBG) is recommended. Please note that further characterization is necessary to subclassify this group.
The cutaneous porphyrias are classified on the basis of the
specific porphyrin identified.
In addition there is a group of acquired hepatic porphyrias.
These porphyrias which are most usually a result of either lead poisoning
or hereditary tyrosinemia.
In lead poisoning, ALA and coproporphyrin are increased. In
determination the use of zinc protoporphyrin (ZPP; or free erythrocyte
porphyrins, FEP) lead levels helps to confirm this diagnosis.
In cases of tyrosinemia the ALA and coproporphyrin are also elevated.
Dr. Robert Johnson M.D.
website brought to by the book...