Cognitive impairments in inherited metabolic diseases: Promises and challenges

Abstract

This is an introduction to the special issue on cognitive impairments in inherited metabolic diseases (IMD). It provides an overview of the studies included, focusing on the possibility of selective impairments which could provide unique evidence on the specificity of neural circuitries mediating cognitive functions. It will suggest that these circuitries have different metabolic properties which make them especially apt to carry out certain functions, but also particularly susceptible to certain forms of metabolic disruption. Knowledge of selective impairments is also crucial to properly evaluate the difficulties engendered by individual diseases and track treatment outcomes. IMR research holds the promise of a more complete understanding of cognition, from cellular functioning to behaviour and of further improvements in treatment. Advances, however, will require detailed assessments, comparisons across diseases, and the integration of different levels of explanation. This will be possible only through close collaborations between centres and types of professionals.

Detailed profile of cognitive dysfunction in children with aspartylglucosaminuria

“…Impairment in executive functions have been reported in other metabolic diseases as well, such as alpha‐mannosidosis and mucopolysaccharidosis II, although the level of impairment and the overall IQ level vary enormously between diseases. In the recent analysis of metabolic diseases, it has been proposed that executive functions rely on extensive brain resources, and the more severe the disease, the more impaired the executive functions . Indeed, major MRI abnormalities in cerebral and cerebellar white and gray matter structures have been reported in AGU patients …”

“…In the recent analysis of metabolic diseases, it has been proposed that executive functions rely on extensive brain resources, and the more severe the disease, the more impaired the executive functions. 18 Indeed, major MRI . D, Illustrates the subtest profiles of two 8-years-old AGU children.…”