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

Abstract

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

Translating principles of precision medicine into speech-language pathology: Clinical trial of a proactive speech and language intervention for infants with classic galactosemia

“… 3 CAS is diagnosed in 24%–63% of children with CG, 5 , 58 , 66 , 69 compared with 0.1%–0.2% of children generally. 4 The fact that the cerebellum has been implicated in CG 70 , 71 may explain the confluence of fine and gross motor delays and CAS. Disordered language is seen in 50%–78% of children with CG, 65 , 66 , 68 compared with 7%–10% of children generally.…”

Neuropsychological stability in classical galactosemia: A pilot study in 10 adult patients

“…Since neuropsychological assessment is sensitive for changes in cognitive functioning due to neurodegeneration in an early stage, 22 an ongoing pathophysiological process causing cognitive decline would likely have been detected by repeated neuropsychological assessment. Therefore, it is more likely that the cognitive impairment in CG originates in earlier developmental stages 23,24 . Importantly, the absence of cognitive decline in adults shows that the adults with normal to borderline intelligence in the current sample in their early and middle adulthood do not cognitively age faster than the general population.…”

“…Therefore, it is more likely that the cognitive impairment in CG originates in earlier developmental stages. 23,24 Importantly, the absence of cognitive decline in adults shows that the adults with normal to borderline intelligence in the current sample in their early and middle adulthood do not cognitively age faster than the general population. Since this study does not include CG-patients with severe intellectual disabilities, no statements can be made about the cognitive aging of severely affected adult patients.…”

Novel imaging technologies for genetic diagnoses in the inborn errors of metabolism

“…Subsequently, using diffusion tensor imaging, others found that compared to age-and gender-matched controls, patients with galactosemia had reduced volume in the left cerebellar white matter, the bilateral putamen, and left superior temporal sulcus. There was also lower fractional anisotropy and higher radial diffusivity values in the dorsal and ventral language networks compared to the controls [17] .…”