acute intermittent porphyria

Last edited 06/2022 and last reviewed 06/2022

Acute intermittent porphyria (AIP) is a particularly severe form of porphyria which results from a deficiency of porphobilinogen deaminase.

• is an autosomal dominant metabolic disorder characterized by a deficiency in heme biosynthesis
• Heme biosynthesis occurs throughout the body, but it is most prominent in the erythroblastic system and liver
  • AIP is a hepatic porphyria whereby the liver is the source of toxic heme metabolites
  • clinical manifestations of AIP result from a genetic mutation that leads to partial function of porphobiliogen deaminase (PBGD)
    • causes an accumulation of upstream, neurotoxic metabolites

In common with the other acute porphyrias the clinical course is one of clinical latency followed by an acute episode following a precipitating event. The main clinical features of an attack are gastrointestinal disturbance and neuropsychiatric disorders

• symptoms include but are not limited to peripheral neuropathies, autonomic neuropathies and psychiatric manifestations
• AIP can be life threatening and clinical signs and symptoms are often heterogeneous and non-specific

Haem infusions

• are presently, in most settings, the preferred specific treatment for sporadic acute attacks (2)
  • haem restores hepatic haem
  • haem infusions are usually well tolerated and successful in the treatment of sporadic acute attacks
  • mechanism of action:
    • to produce haem, the body needs to convert porphyrin precursor chemicals ALA and PBG (5-aminolaevulinic acid and porphobilinogen) into more complicated substances called porphyrins. These are then converted from one type of porphyrin into another to form haem
    • by replenishing hepatic haem stores the initial rate-limiting enzyme ALA synthase is inhibited by a process of negative feedback. The formation of porphyrins and their precursors, ALA and PBG, is reduced and symptoms improve
    • after haem administration, urine ALA, PBG and porphyrins will fall within the first 24 hours

Reference:

• Spiritos Z, Salvador S, Mosquera D, Wilder J. Acute Intermittent Porphyria: Current Perspectives And Case Presentation. Ther Clin Risk Manag. 2019 Dec 16;15:1443-1451. doi: 10.2147/TCRM.S180161. PMID: 31908464; PMCID: PMC6930514.
• Bustad HJ, Kallio JP, Vorland M, Fiorentino V, Sandberg S, Schmitt C, Aarsand AK, Martinez A. Acute Intermittent Porphyria: An Overview of Therapy Developments and Future Perspectives Focusing on Stabilisation of HMBS and Proteostasis Regulators. Int J Mol Sci. 2021 Jan 12;22(2):675. doi: 10.3390/ijms22020675. PMID: 33445488; PMCID: PMC7827610