Brain MRI findings in aspartylglucosaminuria

Tokola, Anna; Åberg, L.; Autti, Taina

doi:10.1016/j.neurad.2015.03.003

Cited by 15 publications

(24 citation statements)

References 28 publications

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“…In every figure "norm mean" stands for the standardized mean and "norm SD" for the standardized score for one SD below the mean abnormalities in cerebral and cerebellar white and gray matter structures have been reported in AGU patients. 20 Previous studies have further suggested that the development of AGU children is associated with slow but advancing development of cognitive skills up to the age of 13 to 15. 3 In the examined AGU children, there were no significant positive correlations between age and raw scores of any subtest indicating that the average cognitive level remains rather stable throughout the school years.…”

Section: Discussionmentioning

confidence: 98%

Detailed profile of cognitive dysfunction in children with aspartylglucosaminuria

Harjunen

Lainé

Tikkanen

et al. 2019

J of Inher Metab Disea

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Aspartylglucosaminuria (AGU) is a rare, recessively inherited lysosomal disease with relatively high prevalence in Finnish population. This progressive disease has a vast impact on patient's cognition and physical health, leading to intellectual disability and shorter life expectancy. Cognitive functions of 21 7‐ to 14‐year‐old children with AGU were studied cross‐sectionally using Wechsler's Intelligence Scale for Children IV and the results were compared with a standardized Finnish sample. In addition to overall cognitive performance, abilities in discrete cognitive domains, including verbal comprehension, perceptual reasoning, working memory, and processing speed, were examined. The results showed that despite the very low overall level of cognitive performance, there were notable differences between individuals. All those children whose performance was closer to their own age level were 7 to 10 years old. Processing speed appeared more compromised, as compared with verbal comprehension. Furthermore, examining the subtest raw scores, there were no significant positive correlations between age and subtest scores, suggesting that the developmental level of AGU children could be rather stable throughout ages 7 to 14. This study gives insight to the severe nature of AGU disease. Since younger children performed better compared to their age norms than older children, the results raise a question whether the highest peak in cognitive functions is reached at an earlier age than previously thought.

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Section: Discussionmentioning

confidence: 98%

Detailed profile of cognitive dysfunction in children with aspartylglucosaminuria

Harjunen

Lainé

Tikkanen

et al. 2019

J of Inher Metab Disea

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“…The skull is often thick and as the patient ages, the loss of brain cells is evident. The disease has a characteristic MRI finding [24]. A special phenomenon is the reduction or shrinking of head circumference as the patient ages (Fig.…”

Section: Clinical Descriptionmentioning

confidence: 99%

Aspartylglycosaminuria: a review

Arvio

Mononen

2016

Orphanet J Rare Dis

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Aspartylglucosaminuria (AGU), a recessively inherited lysosomal storage disease, is the most common disorder of glycoprotein degradation with a high prevalence in the Finnish population. It is a lifelong condition affecting on the patient’s appearance, cognition, adaptive skills, physical growth, personality, body structure, and health. An infantile growth spurt and development of macrocephalia associated to hernias and respiratory infections are the key signs to an early identification of AGU. Progressive intellectual and physical disability is the main symptom leading to death usually before the age of 50 years.The disease is caused by the deficient activity of the lysosomal enzyme glycosylasparaginase (aspartylglucosaminidase, AGA), which leads to a disorder in the degradation of glycoasparagines – aspartylglucosamine or other glycoconjugates with an aspartylglucosamine moiety at their reducing end – and accumulation of these undegraded glycoasparagines in tissues and body fluids. A single nucleotide change in the AGA gene resulting in a cysteine to serine substitution (C163S) in the AGA enzyme protein causes the deficiency of the glycosylasparaginase activity in the Finnish population. Homozygosity for the single nucleotide change causing the C163S mutation is responsible for 98% of the AGU cases in Finland simplifying the carrier detection and prenatal diagnosis of the disorder in the Finnish population. A mouse strain, which completely lacks the Aga activity has been generated through targeted disruption of the Aga gene in embryonic stem cells. These Aga-deficient mice share most of the clinical, histopathologic and biochemical characteristics of human AGU disease. Treatment of AGU mice with recombinant AGA resulted in rapid correction of the pathophysiologic characteristics of AGU in non-neuronal tissues of the animals. The accumulation of aspartylglucosamine was reduced by up to 40% in the brain tissue of the animals depending on the age of the animals and the therapeutic protocol. Enzyme replacement trials on human AGU patients have not been reported so far. Allogenic stem cell transplantation has not proved effective in curing AGU.

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“…The first examination of the affected twin had been included in a previous study (Tokola et al 2015).…”

Section: Visual Analysismentioning

confidence: 99%

“…Previous brain magnetic resonance imaging (MRI) studies have revealed a typical combination of findings in AGU, including decreased T2 signal intensity (SI) in the thalami and especially the pulvinar nuclei, high T2 SI in the periventricular white matter (WM), juxtacortical high T2 SI foci and poor differentiation between gray matter (GM) and WM. Also, thin corpus callosum (CC) and some degree of cerebral and/or cerebellar atrophy are found in nearly all patients with AGU (Autti et al 2008;Tokola et al 2015).…”

Section: Introductionmentioning

confidence: 99%

White Matter Microstructure and Subcortical Gray Matter Structure Volumes in Aspartylglucosaminuria; a 5-Year Follow-up Brain MRI Study of an Adolescent with Aspartylglucosaminuria and His Healthy Twin Brother

Tokola¹,

Brandstack²,

Antti³

et al. 2017

JIMD Reports

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Objective: Aspartylglucosaminuria is an inherited, lysosomal storage disease causing progressive decline in cognitive and motor functions. The aim of this study was to evaluate volumes of subcortical gray matter structures and white matter microstructure in aspartylglucosaminuria in adolescence in a longitudinal study for the first time. Methods: A boy with aspartylglucosaminuria and his healthy twin brother were imaged twice with a 3.0 T MRI scanner at the ages of 10 and 15 years. Subcortical gray matter structure volumes were measured using an atlasbased automatic method, and diffusion tensor imaging was used to evaluate the white matter microstructure of the corpus callosum and the thalamocortical pulvinar tracts. Results: The subcortical gray matter structures were smaller at onset and diminished at follow-up in the affected twin, with the exception of the amygdala which was larger and remained the size. The largest difference in volume between the twins was found in the thalami. The total gray and white matter volumes decreased in the affected twin. In diffusion tensor imaging analysis, the fractional anisotropy was decreased at onset in the affected twin compared to the healthy brother in the evaluated tracts. The axial, radial and mean diffusivity values were increased in the affected twin. The difference between the twins increased slightly at follow-up. Interpretation: The findings suggest that volumetric measurements and diffusion tensor imaging based microstructural analysis may be useful modalities for monitoring disease progression and response to emerging treatment in aspartylglucosaminuria, but further studies with more subjects are necessary to confirm the results.

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Brain MRI findings in aspartylglucosaminuria

Cited by 15 publications

References 28 publications

Detailed profile of cognitive dysfunction in children with aspartylglucosaminuria

Detailed profile of cognitive dysfunction in children with aspartylglucosaminuria

Aspartylglycosaminuria: a review

White Matter Microstructure and Subcortical Gray Matter Structure Volumes in Aspartylglucosaminuria; a 5-Year Follow-up Brain MRI Study of an Adolescent with Aspartylglucosaminuria and His Healthy Twin Brother

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