Case report:
We present the case of a Mexican woman who started experiencing
recurring episodes of intense abdominal pain, weakness in her upper and
lower extremities, uncontrollable vomiting, and insomnia at the age of
17. These symptoms required frequent visits to the emergency department.
Despite undergoing normal biochemical and imaging tests, not responding
to pain relief medications, and even undergoing abdominal surgery for
suspected acute appendicitis, her symptoms persisted. After enduring
nearly three years of almost daily symptoms, an episode of elevated
urine porphobilinogen during a crisis finally confirmed the diagnosis of
acute intermittent porphyria.
Treatment with hematin derivatives (Normosang®, Panhematin®) was
initiated, resulting in partial improvement. However, subsequent years
witnessed progressively severe crises, some accompanied by paralysis and
kidney injury. Remarkably, elevated urine porphobilinogen was even
detected during asymptomatic periods. Notably, her first cousin also
received a diagnosis of acute intermittent porphyria with a similar
clinical presentation.
A molecular genetic study was conducted at a reference center in
Belgium. All coding exons (1, 3-15), including parts of the adjacent
intronic sequences and regions of the 5´- and 3´-UTR of the HMBS gene,
were PCR-amplified from genomic DNA. The amplicons underwent direct
sequencing using capillary electrophoresis and the BigDye technology
(Applied Biosystems). Data alignment and comparison with the wildtype
sequence (NM_000190.3) were performed using the GenBank Database. This
analysis revealed a heterozygous state mutation, c.457C>T
(p.Q153, exon 9, HMBS gene).
At the age of 28, she enrolled in a clinical trial for Givosiran, an RNA
interference therapeutic targeting ALAS1 mRNA. Remarkably, she exhibited
a remarkable response to the treatment and continued it even after the
trial. Over the past years, her symptoms have been sporadic, and she has
not required hospitalization.