Acute intermittent porphyria
The porphyrias are inherited or
acquired disorders of specific enzymes in the heme biosynthetic pathway.
AIP is an autosomal dominant condition resulting from the half-normal level
of HMB synthase (also termed PBG deaminase) activity. The disease is widespread
but is especially common in Scandinavia and perhaps Great Britain.
There may be a family history and this must be a blood relative. Abdominal
pain, nausea, vomiting and loss of appetite are the most frequent symptoms
and are often accompanied by
constipation and a fast pulse rate. The urine
may be dark or it may darken on standing, particularly in sunlight. The
abdominal pain is difficult to describe and does not fit close by descriptions
for other diseases. It is important to avoid any unnecessary surgery in
an attempt to diagnose the cause of the pain.
Most patients with AIP never experience anything more severe than the
symptoms listed above. In rare cases
there will be a change in the level of consciousness
and various abnormalities of mental function. Hyponatremia may occur. The
abdominal pain, vomiting, etc. may become worse. Muscle weakness may develop.
Nerves supplying both muscles and sensation do not conduct properly and
the disturbances of brain function listed above become more severe. Finally,
the muscles that govern breathing may become paralyzed and under these circumstances,
death is possible unless the patient is supported in a hospital.
Recovery from earlier stages of the disease will be
complete. However, if the peripheral nerves have been affected, i.e. if
muscle weakness has developed during the acute attack of AIP, some residual
paralysis may remain and this may take from one-half to three years for
recovery to be complete. In the occasional patient it may never be complete.
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ALA (d-aminolevulinate) and PBG (porphobilinogen) levels are increased
in plasma and urine during acute attacks.
Screening of cases not presenting with an acute attack requires a 24
hour urine collection which can be tested for aminolevulinic acid and porphobilinogen,
but if normal levels are obtained, this does not exclude the possibility
that you carry the gene for the condition. However, a positive test makes
it likely that the patient carries the gene for AIP, provided a stool test
for porphyrins is not abnormal.
A second test can be performed on your blood. This tests for something
called "porphobilinogen deaminase" (also called "uroporphyrinogen synthase")
and about 90% of patients with the gene for AIP show a reduced level of
this. This is called an enzyme test and is only available in a few specialized
laboratories. Measurement of HMB synthase in erythrocytes is useful
to confirm the diagnosis and to screen asymptomatic family members.
During acute attacks, narcotic analgesics may be required for abdominal
pain, and phenothiazines are useful for nausea, vomiting, anxiety, and restlessness.
Intravenous heme is more effective than glucose in reducing porphyrin precursor
excretion and probably leads to more rapid recovery. The response to heme
therapy is reduced if therapy is delayed. Therefore, 3 to 4 mg of heme,
in the form of hematin (Abbott Laboratories), heme albumin, or heme arginate
(Leiras Oy, Turku, Finland), may be infused daily for 4 days beginning as
soon as possible after onset of an attack.
Recovery from severe motor neuropathy may require months or years. Identification
and avoidance of inciting factors can hasten recovery from an attack and
prevent future attacks. Multiple inciting factors may contribute to a symptomatic
episode. Frequent clear-cut cyclical attacks occur in some women and can
be prevented with a long-acting gonadotropin-releasing hormone analogue
(not FDA approved).