Clinical Guidance

No genotype-phenotype correlations have been identified.

Source: GeneReviews — "Acute Intermittent Porphyria"

Penetrance

Penetrance of AIP in heterozygous family members of proband who has experienced manifestations of AIP. The penetrance of AIP-related manifestations is higher in heterozygous family members of an individual who either has symptomatic or asymptomatic acute porphyria or is a high excreter than in heterozygotes in the general population. However, penetrance data vary between studies, as the calculation model, inclusion criteria, and clinical categorization may differ.

Source: GeneReviews — "Acute Intermittent Porphyria"

Diagnostic Criteria

Suggestive Findings

An acute porphyria attack should be suspected in a proband with the following clinical findings and family history or in an individual who experiences two or more of the following clinical findings typically persisting for more than 24 hours in the absence of other likely explanations.

Clinical findings of an acute porphyria attack

Source: GeneReviews — "Acute Intermittent Porphyria"

Differential Diagnosis

Acute neurovisceral attacks. Clinically indistinguishable acute neurovisceral attacks occur in acute intermittent porphyria (AIP) and the other three acute porphyrias and may complicate tyrosinemia type 1 . Table 4. Genetic Disorders in the Differential Diagnosis of Symptomatic Acute Intermittent Porphyria

Management Guidelines

No clinical practice guidelines for acute intermittent porphyria (AIP) have been published.

Initial Evaluations

Evaluations Following Initial Diagnosis of an AIP Attack

To establish the extent of disease and needs in an individual diagnosed with AIP who is experiencing acute manifestations, the following evaluations (if not performed as part of the evaluation that led to the diagnosis) are recommended:

Source: GeneReviews — "Acute Intermittent Porphyria"

Clinical Guidance

Individuals with AIP are advised to avoid excessive alcohol consumption. Alcohol has been shown to upregulate ALAS1, the first enzyme of hepatic heme biosynthesis , and thus could be a trigger for acute attacks. Excessive alcohol use is defined as binge drinking (i.e., consuming four or more drinks on an occasion for a woman or five or more drinks on an occasion for a man) or heavy drinking (i.e., consuming eight or more drinks per week for a woman or fifteen or more drinks per week for a man) (see www.cdc.gov). In all the acute porphyrias, information on the safety of many drugs and other over-the-counter preparations is incomplete; however, evidence-based guidelines for assessment of drug porphyrogenicity have been published .

• For a searchable drug safety database, see the Drug Database.

• See the American Porphyria Foundation drug database.

• For information on prescribing medication in the context of certain conditions (e.g., HIV, epilepsy, malaria), see Porphyria South Africa.

• Safe drug lists are available at Welsh Medicines Information Centre - Porphyria Information Service.

Source: GeneReviews — "Acute Intermittent Porphyria"

Therapies Under Investigation

Search ClinicalTrials.gov in the US and EU Clinical Trials Register in Europe for access to information on clinical studies for a wide range of diseases and conditions. Note: There may not be clinical trials for this disorder.

Source: GeneReviews — "Acute Intermittent Porphyria"

Surveillance Guidelines

Surveillance for All HMBS Heterozygotes Over Age 50 Years

Based on current knowledge, it is not possible to distinguish whether certain groups of individuals who are heterozygous for a pathogenic HMBS variant have an increased risk of developing primary liver cancer (PLC). Therefore, it is recommended that all individuals who are heterozygous for a pathogenic HMBS variant and are over 50 years of age undergo surveillance for PLC, regardless of clinical presentation, PBG excretion level, or how they were brought to the attention of physicians, including but not limited to family screening or genetic testing (such as multigene panel, exome sequencing, or genome sequencing) performed as part of an evaluation for another condition. Most porphyria centers recommend PLC surveillance by annual or twice a year ultrasound examination for all individuals who are heterozygous for a pathogenic HMBS variant starting at age 50 years. Because annual ultrasound surveillance has relatively low sensitivity for early PLC detection and, thus, might be ineffective in high-risk individuals such as those with symptomatic or asymptomatic AIP older than age 50 years who have a persistently high urinary PBG concentration, twice a year surveillance is recommended . Note: Serum alpha-fetoprotein measurement is not helpful in surveillance.

Source: GeneReviews — "Acute Intermittent Porphyria"