Introduction:
Acute intermittent porphyria (AIP) represents an autosomal dominant
disorder stemming from a partial deficiency in the enzymatic activity of
porphobilinogen deaminase, which is also referred to as
hydroxymethylbilane synthase (HMBS), the third enzyme involved in the
synthesis of heme. This deficiency leads to the accumulation of toxic
heme metabolites, namely aminolevulinic acid (ALA) and porphobilinogen
(PBG) (1) The precise mechanisms through which porphyrin precursors
trigger the symptoms of AIP are not fully understood (1,2)
AIP presents with a range of clinical manifestations that can be
categorized into three distinct phases: the prodromal phase, the
visceral symptom phase, and the neurological phase. Prominent clinical
symptoms encompass the occurrence of acute neurovisceral episodes,
marked by intense abdominal pain, mental disturbances, and heightened
sympathetic activity (2)
Acute attacks of porphyria can be precipitated by a range of factors,
encompassing alcohol ingestion, stress, fasting, menstruation, surgical
procedures, infection, and the administration of certain drugs (1,3).
Preliminary assessment for AIP involves the detection of markedly
elevated porphyrin levels in urinary, stool or serum during an acute
attack, followed by subsequent genetic analysis to confirm the presence
of HMBS gene mutations (4). The management of AIP encompasses a
comprehensive approach that includes the management of acute attacks,
prevention of future episodes, long-term monitoring, and the treatment
of associated complications (2).
Among the various acute porphyrias, AIP is recognized as a prevalent
condition on a global scale, being both the most common and severe form
among the acute hepatic porphyrias (5) AIP affects both males and
females, however, in the context of AIP episodes, females tend to
experience more severe impacts in terms of higher frequencies of
attacks, longer durations of attacks, and an increased likelihood of
requiring hospitalization (6).
The HMBS gene is situated at the chromosomal position 11q23.3 and has
been linked to more than 400 pathogenic mutations (5). Individuals
harboring pathogenic variants of the HMBS gene, regardless of their
symptomatic or latent status, are prone to experiencing acute attacks.
Furthermore, chronic complications such as hepatocellular carcinoma,
hypertension, and chronic renal failure can manifest in both symptomatic
individuals with AIP and those who are asymptomatic but carry pathogenic
HMBS variants (7).
To date, limited knowledge exists regarding certain variants of
pathogenic HMBS, particularly in low and middle-income countries such as
Mexico. Consequently, there is uncertainty about the disease behavior in
these individuals. Further research is warranted to address these gaps
and enhance our understanding of AIP management in this specific patient
population.