Neuroenergetic Changes in Patients with X-Linked Dystonia-Parkinsonism and Female Carriers

Mov Disord Clin Pract. 2024 May;11(5):550-555. doi: 10.1002/mdc3.14001. Epub 2024 Feb 25.

Abstract

Background: X-linked dystonia-parkinsonism (XDP) is a rare movement disorder characterized by profound neurodegeneration in the basal ganglia. The molecular consequences and the bioenergetic state of affected individuals remain largely unexplored.

Objectives: To investigate the bioenergetic state in male patients with XDP and female carriers using 31phosphorus magnetic resonance spectroscopy imaging and to correlate these findings with clinical manifestations.

Methods: We examined the levels of high-energy phosphorus-containing metabolites (HEP) in the basal ganglia and cerebellum of five male patients with XDP, 10 asymptomatic female heterozygous carriers, and 10 SVA-insertion-free controls.

Results: HEP levels were reduced in the basal ganglia of patients with XDP (PwXDP) compared to controls, but increased in the cerebellum of both male patients and female carriers.

Conclusions: Our findings suggest a potential compensatory mechanism in the cerebellum of female carriers regardless of sex. Our study highlights alterations in HEP levels in PwXDP patients and female carriers.

Keywords: 31‐phosphorus magnetic resonance spectroscopy imaging (31P‐MRSI); TAF1; X‐linked dystonia‐parkinsonism (XDP); neuroimaging.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Basal Ganglia* / diagnostic imaging
  • Basal Ganglia* / metabolism
  • Cerebellum* / diagnostic imaging
  • Cerebellum* / metabolism
  • Cerebellum* / pathology
  • Dystonic Disorders* / diagnostic imaging
  • Dystonic Disorders* / genetics
  • Dystonic Disorders* / metabolism
  • Dystonic Disorders* / pathology
  • Dystonic Disorders* / physiopathology
  • Energy Metabolism
  • Female
  • Genetic Diseases, X-Linked* / genetics
  • Genetic Diseases, X-Linked* / metabolism
  • Genetic Diseases, X-Linked* / pathology
  • Genetic Diseases, X-Linked* / physiopathology
  • Heterozygote*
  • Humans
  • Magnetic Resonance Spectroscopy
  • Male
  • Middle Aged
  • Young Adult

Supplementary concepts

  • Dystonia 3, Torsion, X-Linked