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

J Inherit Metab Dis. 2020 Nov;43(6):1205-1218. doi: 10.1002/jimd.12279. Epub 2020 Aug 3.


Classic galactosemia (OMIM# 230400) is an autosomal recessive disorder due to galactose-1-phosphate uridyltransferase deficiency. Newborn screening and prompt treatment with a galactose-free diet prevent the severe consequences of galactosemia, but clinical outcomes remain suboptimal. Five men and five women with classic galactosemia (mean age = 27.2 ± 5.47 years) received comprehensive neurological and neuropsychological evaluations, electroencephalogram (EEG) and magnetic resonance imaging (MRI). MRI data from nine healthy controls (mean age = 30.22 ± 3.52 years) were used for comparison measures. Galactosemia subjects experienced impaired memory, language processing, visual-motor skills, and increased anxiety. Neurological examinations revealed tremor and dysarthria in six subjects. In addition, there was ataxia in three subjects and six subjects had abnormal gait. Mean full scale IQ was 80.4 ± 17.3. EEG evaluations revealed right-sided abnormalities in five subjects and bilateral abnormalities in one subject. Compared to age- and gender-matched controls, subjects with galactosemia had reduced volume in left cerebellum white matter, bilateral putamen, and left superior temporal sulcus. Galactosemia patients also had lower fractional anisotropy and higher radial diffusivity values in the dorsal and ventral language networks compared to the controls. Furthermore, there were significant correlations between neuropsychological test results and the T1 volume and diffusivity scalars. Our findings help to identify anatomic correlates to motor control, learning and memory, and language in subjects with galactosemia. The results from this preliminary assessment may provide insights into the pathophysiology of this inborn error of metabolism.

Keywords: MRI; galactosemia; inborn error of metabolism; neuroimaging; tractography.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Anisotropy
  • Brain Mapping / methods*
  • Case-Control Studies
  • Diffusion Magnetic Resonance Imaging / methods*
  • Electroencephalography
  • Female
  • Galactosemias / pathology*
  • Galactosemias / physiopathology
  • Galactosemias / psychology
  • Humans
  • Language
  • Male
  • Motor Activity
  • Neurites / pathology*
  • Neuropsychological Tests
  • White Matter / pathology*
  • White Matter / physiopathology
  • Young Adult