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Acute Intermittent Porphyria.

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GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2014.

Excerpt

DISEASE CHARACTERISTICS:

Acute intermittent porphyria (referred to as AIP in this GeneReview) results from half-normal activity of the enzyme hydroxymethylbilane synthase (HMBS). It is characterized clinically by life-threatening acute neurovisceral attacks of severe abdominal pain without peritoneal signs, often accompanied by nausea, vomiting, tachycardia, and hypertension. Attacks may be complicated by neurologic findings (mental changes, convulsions, and peripheral neuropathy that may progress to respiratory paralysis), and hyponatremia. Acute attacks, which may be provoked by certain drugs, alcoholic beverages, endocrine factors, calorie restriction, stress, and infections, usually resolve within two weeks. Most individuals with AIP have one or a few attacks; about 5% (mainly women) have recurrent attacks (defined as >4 attacks/year) that may persist for years. Other long-term complications are chronic renal failure, hepatocellular carcinoma (HCC), and hypertension. Attacks, which are very rare before puberty, are more common in women than men. All individuals with a genetic change in the gene HMBS that predisposes to AIP are at risk of developing acute attacks; however, most never have symptoms and are said to have latent (or presymptomatic) AIP.

DIAGNOSIS/TESTING:

With one exception (5-aminolevulinate dehydratase deficiency [ALAD]), acute attacks of porphyria are associated with an increased urinary concentration of porphobilinogen (PBG). Demonstration that an increased PBG concentration is caused by AIP requires exclusion of other acute porphyrias by analysis of porphyrins in stool and plasma. Molecular genetic testing is used in a symptomatic individual to identify a mutation that can then be used to identify AIP in relatives of the proband. Assay of erythrocyte HMBS enzyme activity may be useful in families in which an HMBS mutation cannot be identified or when molecular testing is not available.

MANAGEMENT:

Treatment of manifestations: Acute neurovisceral attacks: Stop medications that can exacerbate AIP; provide adequate caloric intake by intravenous infusion if required (hypotonic dextrose water solutions should be avoided). Treat any intercurrent infections or disease using drugs known to be safe in acute porphyria. Treat pain with opiate analgesia (often in large amounts); support from a pain team may be required. Treat agitation, vomiting, hypertension, tachycardia using safe drugs. Monitor fluid balance and correct electrolyte disturbances, especially hyponatremia; treat severe hyponatremia with saline infusions, not fluid restriction. Monitor neurologic status carefully and provide respiratory support as needed. Prompt administration of human hemin (panhematin or heme arginate) is the specific treatment of choice to curtail acute neurovisceral attacks and avoid paresis. Mild attacks: Manage by symptomatic treatment, increased calorie intake, and fluid replacement. Recurrent acute attacks: Manage together with a porphyria specialist; treatment options include ovulation suppression with gonadorelin analogues, regular hematin infusions, or (as a last resort) liver transplantation. Evaluation of relatives at risk: If the HMBS mutation is known in a family, at-risk relatives can benefit from molecular genetic testing to clarify their genetic status, so that those at increased risk of developing acute attacks of AIP can be identified early and counseled about preventive measures. Prevention of primary manifestations: All individuals with latent porphyria, the parents of affected individuals, and patients in remission should be advised about measures that diminish the risk of acute attacks: Avoid precipitating factors (unsafe prescribed and illicit drugs, excessive alcohol consumption, smoking, and severe calorie restriction). Adopt safe practices (maintenance of a regular, balanced diet; prompt treatment of infections; and reduction of stress). Prevention of secondary complications: Patients treated regularly with heme arginate require monitoring of iron status to detect iron overload. Surveillance: Individuals who have experienced acute attacks require monitoring of renal function; in some countries annual hepatic imaging to detect HCC is also offered to all individuals with an HMBS mutation after age 50 years (whether or not they have experienced acute attacks).

GENETIC COUNSELING:

AIP is inherited in an autosomal dominant manner. About 1% of probands may have a de novo mutation. Sibs and offspring of individuals with an HMBS mutation are at 50% risk of inheriting the HMBS mutation; however, because penetrance is low the likelihood of an individual with an inherited HMBS mutation having an acute attack is small. Prenatal testing is possible but is rarely requested because of the low clinical penetrance and favorable clinical outcome for the great majority of symptomatic adults.

Copyright © 1993-2014, University of Washington, Seattle. All rights reserved.

PMID:
20301372
[PubMed]
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