Acute intermittent porphyria

Definition

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.

Symptoms

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.

Diagnosis

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.

Treatment

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).

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