Clinical Guidance

Acute intermittent porphyria (AIP), caused by a heterozygous HMBS pathogenic variant, is divided into clinical designations based on clinical history (i.e., the number of acute porphyria attacks experienced previously) and urine porphobilinogen (PBG)-to-creatinine ratio .

Table 2.

Acute Intermittent Porphyria: Clinical Designations

Clinical Designation | Individual Who is Heterozygous for an HMBS Pathogenic Variant Associated with AIP and Has Experienced:

Active (symptomatic) AIP

| ≥1 acute porphyria attack in the last 2 years. Active (symptomatic) AIP includes:

• Sporadic AIP (individual has experienced 1 to ≤ 3 acute porphyria attacks);

• Recurrent AIP (individual has experienced ≥4 acute porphyria attacks in a maximum period of 12 mos within the last 2 yrs).

Symptomatic high excreter

| Chronic porp...

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"

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

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"