Hemophagocytic lymphohistiocytosis following gene replacement therapy in a child with type 1 spinal muscular atrophy

Francesca Galletta; Ugo Cucinotta; Lucia Marseglia; Annalisa Cacciola; Romina Gallizzi; Salvatore Cuzzocrea; Sonia Messina; Antonio Toscano; Eloisa Gitto

doi:10.1111/jcpt.13733

Hemophagocytic lymphohistiocytosis following gene replacement therapy in a child with type 1 spinal muscular atrophy

J Clin Pharm Ther. 2022 Sep;47(9):1478-1481. doi: 10.1111/jcpt.13733. Epub 2022 Aug 4.

Authors

Francesca Galletta¹, Ugo Cucinotta¹, Lucia Marseglia¹, Annalisa Cacciola¹, Romina Gallizzi², Salvatore Cuzzocrea³, Sonia Messina⁴, Antonio Toscano⁴, Eloisa Gitto¹

Affiliations

¹ Neonatal and Pediatric Intensive Care Unit, University of Messina, Messina, Italy, Department of Human Pathology in Adult and Developmental Age, University of Messina, Messina, Italy.
² Pediatric Unit, Department of Medical of Health Sciences, Magna Graecia University, Catanzaro, Italy.
³ Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, Messina, Italy.
⁴ Unit of Neurology and Neuromuscular Diseases, Department of Clinical and Experimental Medicine, University of Messina, Messina, Italy.

PMID: 35924856
DOI: 10.1111/jcpt.13733

Abstract

What is known and objective: Onasemnogene abeparvovec (OA) is the first gene replacement therapy for the treatment of paediatric patients with bi-allelic mutations in the SMN1 gene. Efficacy and safety of OA have been assessed in several studies with promising results, despite rare side effects have been described.

Case summary: A 3-year-old child with spinal muscular atrophy was treated with OA and subsequently developed fever, widespread erythematous skin lesions and hepatosplenomegaly. Laboratory tests were suggestive for Hemophagocytic lymphohistiocytosis (HLH).

What is new and conclusion: To our knowledge, this is the first case of HLH following gene replacement therapy with OA, described in literature.

Keywords: hemophagocytic lymphohistiocytosis; onasemnogene abeparvovec; spinal muscular atrophy.

Publication types

Case Reports

MeSH terms

Child
Child, Preschool
Genetic Therapy / adverse effects
Genetic Therapy / methods
Humans
Lymphohistiocytosis, Hemophagocytic* / drug therapy
Lymphohistiocytosis, Hemophagocytic* / therapy
Muscular Atrophy, Spinal* / genetics
Muscular Atrophy, Spinal* / therapy
Mutation