Identification of neuronal structures and pathways corresponding to clinical functioning in galactosemia

Area of Science:

• Neuroscience
• Metabolic Disorders
• Genetics

Background:

• Classic galactosemia is an autosomal recessive disorder caused by galactose-1-phosphate uridyltransferase deficiency.
• While newborn screening and dietary management improve outcomes, significant clinical deficits persist in affected individuals.

Purpose of the Study:

• To investigate the neuroanatomical and neurophysiological correlates of persistent cognitive and motor impairments in adults with classic galactosemia.
• To identify specific brain structure and network alterations associated with galactosemia.

Main Methods:

• Comprehensive neurological and neuropsychological evaluations were performed on ten adult patients with classic galactosemia.
• Electroencephalogram (EEG) and magnetic resonance imaging (MRI) including diffusion tensor imaging were conducted.
• MRI data were compared to nine age- and gender-matched healthy controls.

Main Results:

• Galactosemia patients exhibited impaired memory, language processing, visual-motor skills, and increased anxiety, with neurological signs like tremor, dysarthria, ataxia, and abnormal gait.
• MRI revealed reduced white matter volume in the left cerebellum, bilateral putamen, and left superior temporal sulcus in patients.
• Diffusion imaging showed altered fractional anisotropy and radial diffusivity in language networks, correlating with neuropsychological test results.

Conclusions:

• Structural and functional brain alterations in motor control, learning, memory, and language networks are evident in adults with classic galactosemia.
• These findings provide insights into the pathophysiology of galactosemia and highlight the need for continued research into long-term outcomes and potential interventions.