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.

Recovery of chronic motor neuropathy due to acute intermittent porphyria after givosiran treatment in a young boy: a case report / Mazzoli, M.; Ricci, A.; Vaudano, A. E.; Marcacci, M.; Marchini, S.; Bergonzini, P.; DI PIERRO, E.; Pischik, E.; Iughetti, L.; Pietrangelo, A.; Meletti, S.; Ventura, P.. - In: EUROPEAN REVIEW FOR MEDICAL AND PHARMACOLOGICAL SCIENCES. - ISSN 2284-0729. - 28:8(2024), pp. 3268-3274. [10.26355/eurrev_202404_36055]

Recovery of chronic motor neuropathy due to acute intermittent porphyria after givosiran treatment in a young boy: a case report

M. MAZZOLI
Writing – Original Draft Preparation
;
A. RICCI
Writing – Original Draft Preparation
;
A. E. VAUDANO
Membro del Collaboration Group
;
S. MARCHINI
Data Curation
;
L. IUGHETTI
Membro del Collaboration Group
;
A. PIETRANGELO
Supervision
;
S. MELETTI
Writing – Review & Editing
;
P. VENTURA
Writing – Original Draft Preparation
2024

Abstract

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.
2024
2024
28
8
3268
3274
Recovery of chronic motor neuropathy due to acute intermittent porphyria after givosiran treatment in a young boy: a case report / Mazzoli, M.; Ricci, A.; Vaudano, A. E.; Marcacci, M.; Marchini, S.; Bergonzini, P.; DI PIERRO, E.; Pischik, E.; Iughetti, L.; Pietrangelo, A.; Meletti, S.; Ventura, P.. - In: EUROPEAN REVIEW FOR MEDICAL AND PHARMACOLOGICAL SCIENCES. - ISSN 2284-0729. - 28:8(2024), pp. 3268-3274. [10.26355/eurrev_202404_36055]
Mazzoli, M.; Ricci, A.; Vaudano, A. E.; Marcacci, M.; Marchini, S.; Bergonzini, P.; DI PIERRO, E.; Pischik, E.; Iughetti, L.; Pietrangelo, A.; Meletti, S.; Ventura, P.
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