BACKGROUND: We describe
the first case of a pediatric patient with acute
intermittent porphyria and severe chronic porphyric
neuropathy treated with givosiran, a
small-interfering RNA that drastically decreases
delta-aminolevulinic acid production and reduces
porphyric attacks’ recurrence.
CASE REPORT: A 12-year-old male patient
with refractory acute intermittent porphyria and
severe porphyric neuropathy was followed prospectively
for 12 months after givosiran initiation
(subcutaneous, 2.5 mg/kg monthly). Serial
neurological, structural, and resting-state
functional magnetic resonance imaging (MRI)
evaluations were performed, including clinical
scales and neurophysiological tests. Delta-aminolevulinic
acid urinary levels dropped drastically
during treatment. In parallel, all the administered
neurological rating scales and neurophysiological
assessments showed improvement
in all domains. Moreover, an improvement
in central motor conduction parameters and
resting-state functional connectivity in the sensory-
motor network was noticed. At the end of
the follow-up, the patient could walk unaided after
using a wheelchair for 5 years.
CONCLUSIONS: A clear beneficial effect of
givosiran was demonstrated in our patient with
both clinical and peripheral nerve neurophysiologic
outcome measures. Moreover, we first reported
a potential role of givosiran in recovering
central motor network impairment in acute intermittent
porphyria (AIP), which was previously
unknown. This study provides Class IV evidence
that givosiran improves chronic porphyric neuropathy
