Fabry Disease With Concomitant Lewy Body Disease

Area of Science:

• Neuropathology
• Lysosomal Storage Disorders
• Neurodegenerative Diseases

Background:

• Fabry disease (FD) is a progressive multisystem lysosomal storage disorder.
• Lewy pathology (LP) and extrapyramidal symptoms are known in Gaucher disease.
• The presence of LP in FD remains unexplored.

Purpose of the Study:

• To investigate the co-occurrence and distribution of FD-related inclusions and Lewy pathology (LP) in the brain of an FD patient.
• To compare neuropathological findings with controls and another FD patient.

Main Methods:

• Immunohistochemistry (CD77, α-synuclein, collagen IV) on brain sections.
• Neuropathological staging for LP and evaluation of inclusion body pathology.
• Examination of a 58-year-old FD patient with hypokinesia, a 50-year-old FD patient, and age-matched controls.

Main Results:

• Severe neuronal loss in the substantia nigra pars compacta and LP (Parkinson disease stage 4) were found in the 58-year-old FD patient.
• No LP was detected in the 50-year-old FD patient or controls.
• The affected FD patient had no major cerebrovascular lesions or other significant pathologies.

Conclusions:

• Lewy body disease with parkinsonism can manifest in individuals with Fabry disease.
• Further studies in larger FD cohorts are necessary to determine the frequency of these pathologies.
• Clarifying the implications of these co-occurring lesions for disease pathogenesis and treatment is crucial.