Acute intermittent porphyria
At a minimum, these SNPs are known to be related, and others may also be
AIP is a metabolic disease with a genetic cause. Defects in enzymes required for the synthesis of the vital heme molecule cause variable symptoms. There are over 300 mutations associated with AIP, particularly in the HMBS gene, which codes for the 3rd step in heme production. The condition is characterized by intermittent and sometimes life-threatening acute neurovisceral attacks of severe abdominal pain without peritoneal signs. However, most people who inherit an AIP-associated HMBS mutation never develop symptoms.
A ClinGen Actionability summary (see Actionability (ClinGen)) providing recommendations for individuals with an AIP-associated HMBS mutation is available here.
In brief, the recommendations are (1) periodic (annual) liver ultrasound should be considered for individuals aged >50 years with previous overt or asymptomatic disease who ask to be tested after careful discussion of the likely risks and benefits, (2) patients should avoid alcohol, smoking, medications, and illicit drugs to reduce the risk of attacks, and (3) patients should understand the risks and benefits associated with using hemin in the event of an attack.
Additional resources about acute intermittent porphyria include:
- Rare Disease Network Porphyria Consortium
- Porphyria Consortium AIP page
