Multicentric Retrospective Evaluation of Five Classic Infantile Pompe Disease Subjects Under Enzyme Replacement Therapy With Early Infratentorial Involvement

Matteo Paoletti; Anna Pichiecchio; Giovanna Stefania Colafati; Giorgio Conte; Federica Deodato; Serena Gasperini; Francesca Menni; Francesca Furlan; Laura Rubert; Fabio Maria Triulzi; Claudia Cinnante

doi:10.3389/fneur.2020.569153

Multicentric Retrospective Evaluation of Five Classic Infantile Pompe Disease Subjects Under Enzyme Replacement Therapy With Early Infratentorial Involvement

Front Neurol. 2020 Nov 25:11:569153. doi: 10.3389/fneur.2020.569153. eCollection 2020.

Authors

Affiliations

¹ Advanced Imaging and Radiomics Center, Neuroradiology Department, Istituto di Ricovero e Cura a Carattere Scientifico Mondino Foundation, Pavia, Italy.
² Department of Brain and Behavioral Sciences, University of Pavia, Pavia, Italy.
³ Oncological Neuroradiology Unit, Imaging Department, Istituto di Ricovero e Cura a Carattere Scientifico Ospedale Pediatrico Bambino Gesù, Rome, Italy.
⁴ Fondazione Istituto di Ricovero e Cura a Carattere Scientifico Ca' Granda Ospedale Maggiore Policlinico, Neuroradiology Unit, Milan, Italy.
⁵ Unit of Metabolic Disease, Istituto di Ricovero e Cura a Carattere Scientifico Ospedale Pediatrico Bambino Gesù, Rome, Italy.
⁶ Pediatric Rare Diseases Unit, Department of Pediatrics, Fondazione Monza e Brianza per il Bambino e la sua Mamma, San Gerardo Hospital, Monza, Italy.
⁷ Pediatric Highly Intensive Care Unit, Department of Pathophysiology and Transplantation, University of Milan, Istituto di Ricovero e Cura a Carattere Scientifico Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy.
⁸ Division of Inherited Metabolic Diseases, Department of Diagnostic Services, University Hospital of Padua, Padua, Italy.
⁹ Department of Pathophysiology and Transplantation, University of Milan, Milan, Italy.

Abstract

White matter (WM) abnormalities and ventricular enlargement in brain MRI are well-known features in infantile-onset Pompe disease (IOPD) in the era of enzyme replacement therapy (ERT). In this multicentric observational retrospective study, we report a small cohort of IOPD subjects under ERT treatment (n = 5, median age at MRI = 7.4 years, median period of treatment = 85 months) that showed the classic features of extensive supratentorial WM abnormalities but also unusual findings such as early infratentorial WM abnormalities and late supratentorial U-fiber involvement. Given the recent implementation of ERT and the rarity of the disease, a complete spectrum of presentation and understanding of progressive pathology in the brain of IOPD subjects in treatment remains underacknowledged. The availability of long-term follow-up of IOPD subjects under ERT treatment allows a better insight into the evolution of brain abnormalities in such disease.

Keywords: ERT (enzyme replacement therapy); IOPD; Pompe disease; brain MRI; infantile-onset Pompe disease; white matter (WM).