Neuropathological Characterisation of McLeod Syndrome With a Proposed New Grading System

Area of Science:

• Neuroscience
• Neuropathology
• Genetics

Background:

• X-linked McLeod neuroacanthocytosis syndrome (MLS) is a rare neurodegenerative disorder.
• It presents with red blood cell acanthocytosis and chorea syndrome.
• MLS shares cognitive, behavioral, and movement disorder symptoms with Huntington's disease (HD).

Purpose of the Study:

• To describe the neuropathology of MLS.
• To analyze the largest case series of MLS patients to date.
• To propose a neuropathological grading system for MLS.

Main Methods:

• Collected clinical data from eight male MLS patients.
• Performed neuropathological assessments on patient samples.
• Included patients from Finland, New Zealand, Switzerland, Scotland, and the United States.

Main Results:

• Macroscopic analysis showed basal ganglia atrophy in five of six patients, most pronounced in the caudate nucleus.
• Histology revealed neuronal loss and gliosis in the basal ganglia of all patients.
• A decreasing gradient of severity was observed from the caudate nucleus to the putamen and pallidum; intraneuronal vacuoles were found in the striatum of half the patients.

Conclusions:

• MLS neuropathology is characterized by basal ganglia atrophy, neuronal loss, and gliosis.
• A severity gradient exists from the caudate nucleus to the putamen and pallidum.
• A standardized neuropathological grading system for MLS is proposed, analogous to HD, to aid assessment of this rare disease.