Emerging Pathogenic Variant of ATP13A2 Gene  Associated with Early-Onset Parkinsonism: Insights, Implications, and Literature Review

Affronte Leonardo; Pini Antonella; Pizzoli Claudia; Mazzone Serena; Golemi Arber; Giannotta Melania; Cordelli Duccio Maria; Emanuele Coccia; Valerio Carelli; Vaisfeld Alessandro; Palombo Flavia

Emerging Pathogenic Variant of ATP13A2 Gene Associated with Early-Onset Parkinsonism: Insights, Implications, and Literature Review

by Affronte Leonardo^1,2, Pini Antonella^2*, Pizzoli Claudia³, Mazzone Serena³, Golemi Arber⁵, Giannotta Melania², Cordelli Duccio Maria^3,4, Emanuele Coccia⁶, Valerio Carelli^4,7, Vaisfeld Alessandro⁶, Palombo Flavia⁷

¹Dipartimento di Scienze Mediche e Chirurgiche (DIMEC), Alma Mater Studiorum, Università di Bologna, Italy

²IRCCS Istituto delle Scienze Neurologiche di Bologna, Pediatric Neuromuscular Unit, UO Neuropsichiatria dell’Età Pediatrica, Italy

³IRCCS Istituto delle Scienze Neurologiche di Bologna, UOC Neuropsichiatria dell’Età Pediatrica, Bologna, Italy

⁴Department of Biomedical and Neuromotor Sciences, University of Bologna, Bologna, Italy

⁵Medicina Nucleare, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy

⁶UO Genetica Medica, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy

⁷IRCCS Istituto delle Scienze Neurologiche di Bologna, Programma di Neurogenetica, Bologna, Italy

*Corresponding author: Pini Antonella, IRCCS Istituto delle Scienze Neurologiche di Bologna, Pediatric Neuromuscular Unit, UO Neuropsichiatria dell’Età Pediatrica, Italy

Received Date: 05 July 2024

Accepted Date: 15 July 2024

Published Date: 18 July 2024.

Citation: Leonardo A, Antonella P, Claudia P, Serena M, Arber G, et al. (2024) Emerging Pathogenic Variant of ATP13A2 Gene Associated with Early-Onset Parkinsonism: Insights, Implications, and Literature Review. Arch Pediatr 9: 315. https://doi.org/10.29011/2575825X.100315

Abstract

ATP13A2 is a gene localized on chromosome 1p36.13 and coding for a transmembrane protein found in the lysosomes and late endosomes, which is involved in many cellular metabolic activities. Pathogenetic variants of ATP13A2 are associated with a wide range of neurodegenerative disorder including Kufor Rakeb syndrome (KRS), a rare autosomal recessive form of levodopa responsive juvenile onset parkinsonism (PARK9) characterized by rapidly progressive muscular stiffness, bradykinesia, spasticity, pyramidal findings, dementia and supranuclear gaze palsy.

The aim of this study is to provide detailed clinical descriptions of two siblings, carriers of biallelicATP13A2 variants. One of them showed KRS motor features at the age of 10 and mild developmental delay as first clinical finding at 2 years, while the other only showed cognitive impairment at our last evaluation at 11 years of age. Additionally, we reviewed the previously published cases, focusing on early signs and symptoms, clinical evolution and response to therapy. To our knowledge, this is the only work that groups all reported KRS patients and compares their clinical and molecular features.

Keywords: ATP13A2; Jenile onset parkinsonism, Kufor Rakeb syndrome