This page has moved. Click here to view.

ACUTE INTERMITTENT PORPHYRIA

Acute intermittent porphyria is an autosomal dominant disorder that results from an approximately 50% acute intermittent porphyria, porfiria, porphria, porphiria deficiency of PBG deaminase. The enzyme is deficient in all individuals who inherit the mutant gene and remains fairly constant over time. The majority of subjects with PBG deaminase deficiency remain

ETIOLOGY AND PATHOGENESIS.

More than 100 different mutations of the PBG deaminase gene have been identified in unrelated AIP lineages. Two isoenzymes of PBG deaminase are known, an erythroid-specific and a non-erythroid or "housekeeping" form. Both are transcribed by alternative mRNA splicing from the same gene, which contains 15 exons. The erythroid-specific isoenzyme is encoded by exons 2 to 15; the erythroid promoter, which functions only in erythroid cells, is found immediately upstream from exon 2. The

CLINICAL MANIFESTATIONS.

Symptoms rarely occur before puberty and seldom if ever recur throughout adult life. Characteristically, attacks last for several days or longer, often require hospitalization, and are followed by complete recovery. Abdominal pain is the most common symptom, is usually steady and poorly localized, but may be cramping. Tachycardia, hypertension, restlessness, fine tremors, and excess sweating may be due to sympathetic overactivity. Other manifestations include nausea and vomiting; constipation; pain in

Peripheral neuropathy in AIP is primarily motor, results from axonal degeneration, and does not develop in all patients with acute attacks, even when abdominal symptoms are severe. Rarely, neuropathy develops apart from abdominal symptoms. Weakness

The central nervous system can be involved. Anxiety, insomnia, depression, disorientation, hallucinations, and paranoia, which

PRECIPITATING FACTORS.

Recognition of precipitating factors is important in management. Endogenous steroid hormones are probably most important. AIP is characterized by rarity of symptoms and excess ALA and PBG before puberty, more frequent clinical expression in women, premenstrual attacks in some women, and exacerbations after the administration of sex steroid preparations. Some patientsremesis gravidarum and reduced caloric intake.

Drugs remain important as causes of AIP attacks. Published information is insufficient to allow most drugs to be classified as definitely harmful or safe. The major drugs known to be harmful or safe in the acute porphyrias are listed. Barbiturates and sulfonamides are the

Benzodiazepines are much less hazardous. Some drugs may exacerbate porphyria cutanea tarda (PCT) but not acute porphyrias (see below). Advice can be sought from a center with experience in porphyria with regard to the use of 

Reduced caloric intake, usually instituted in an effort to lose weight, is a common cause of attacks. Attacks are also provoked by intercurrent infections, major surgery, and other conditions. Cigarette smoke contains chemicals that can induce hepatic heme

TREATMENT.

Acute attacks usually require hospitalization for the treatment of severe pain, nausea, and vomiting and for the administration of intravenous glucose and heme. Hospitalization also facilitates observation for neurologic complications, electrolyte imbalances, and nutritional status, as well as investigation of precipitating factors. Symptomatic therapy includes narcotic analgesics, which are usually required for abdominal pain, and small to moderate doses of a phenothiazine for nausea, vomiting, anxiety, and

Heme therapy and carbohydrate loading are specific therapies because they repress hepatic ALA synthase and overproduction of ALA and PBG. Heme therapy is most effective in this regard and should be initiated early, but only after the diagnosis of a

The standard regimen for heme therapy is 3-4 mg heme per kilogram body weight infused intravenously once daily for 4 days. A longer course of treatment is seldom necessary if treatment is started early. Efficacy is reduced and recovery less rapid when

Carbohydrate loading may suffice for mild attacks and can be given orally as sucrose, glucose polymers, or carbohydrate-rich

Treatment of seizures is problematic because almost all antiseizure drugs can exacerbate AIP. Bromides, gabapentin, and