CASE REPORT article

Front. Genet.

Sec. Genetics of Common and Rare Diseases

Volume 16 - 2025 | doi: 10.3389/fgene.2025.1588812

This article is part of the Research TopicDementia and Movement Disorders: Integrated Genetic Insights and Advanced Diagnostic ApproachesView all articles

Case report: Novel ATP13A2 pathogenic variants associated with early-onset parkinsonism and a mini-review

Provisionally accepted
Leonardo AffronteLeonardo Affronte1,2Antonella PiniAntonella Pini2*Pizzoli ClaudiaPizzoli Claudia3Emanuele CocciaEmanuele Coccia4Serena MazzoneSerena Mazzone3Arber GolemiArber Golemi5Melania GiannottaMelania Giannotta2Duccio Maria CordelliDuccio Maria Cordelli3,6Valerio CarelliValerio Carelli6,7Alessandro VaisfeldAlessandro Vaisfeld4,8Flavia PalomboFlavia Palombo7
  • 1Department of Medical and Surgical Sciences, Alma Mater Studiorum – Università di Bologna, Bologna, Emilia-Romagna, Italy
  • 2IRCCS Istituto delle Scienze Neurologiche di Bologna, Pediatric Neuromuscular Unit, UO Neuropsichiatria dell’Età Pediatrica, Bologna, Italy, Bologna, Italy
  • 3IRCCS Istituto delle Scienze Neurologiche di Bologna, UOC Neuropsichiatria dell'Età Pediatrica, Bologna, Italy, Bologna, Italy
  • 4Medical Genetics Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy, Bologna, Italy
  • 5Medicina Nucleare, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy, Bologna, Italy
  • 6Department of Biomedical and Neuromotor Sciences, University of Bologna, Bologna, Emilia-Romagna, Italy
  • 7IRCCS Istituto delle Scienze Neurologiche di Bologna, Programma di Neurogenetica, Bologna, Italy, Bologna, Italy
  • 8Department of Internal Medicine and Surgery, University of Bologna, Bologna, Emilia-Romagna, Italy

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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 (MxMD-ATP13A2), 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 novel biallelic ATP13A2 variants. One of them showed KRS levodopa-responsive motor dystonic features at the age of 10 years preceded by moderate cognitive impairment, while the other only showed mild 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, WES, juvenile onset parkinsonism, Kufor Rakeb syndrome, KRS cases revision

Received: 06 Mar 2025; Accepted: 10 Jul 2025.

Copyright: © 2025 Affronte, Pini, Claudia, Coccia, Mazzone, Golemi, Giannotta, Cordelli, Carelli, Vaisfeld and Palombo. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

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

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