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Gropman et al. J Transl Genet Genom 2020;4:429-45 Journal of Translational
DOI: 10.20517/jtgg.2020.09 Genetics and Genomics

Review Open Access

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

Andrea L. Gropman , Afrouz Anderson 2
1
1 Department of Neurology, Children’s National Medical Center, Washington, DC 20010, USA.
2 Department of Research, Focus Foundation, Crofton, MD 21035, USA.
Correspondence to: Dr. Andrea L. Gropman, Department of Neurology, Children’s National Medical Center, Washington, DC
20010, USA. E-mail: agropman@childrensnational.org
How to cite this article: Gropman AL, Anderson A. Novel imaging technologies for genetic diagnoses in the inborn errors of
metabolism. J Transl Genet Genom 2020;4:429-45. http://dx.doi.org/10.20517/jtgg.2020.09
Received: 3 Feb 2020 First Decision: 4 Mar 2020 Revised: 15 Sep 2020 Accepted: 26 Oct 2020 Available online: 13 Nov 2020

Academic Editor: Tjitske Kleefstra Copy Editor: Cai-Hong Wang Production Editor: Jing Yu

Abstract
Many inborn errors of metabolism and genetic disorders affect the brain. The brain biochemistry may differ from
that in the periphery and is not accessible by simple blood and urine sampling. Therefore, neuroimaging has
proven to be a valuable tool to not only evaluate the brain structure, but also biochemistry, blood flow and function.
Neuroimaging in patients with inborn errors of metabolism can include additional sequences in addition to T1
and T2-weighted imaging because in early stages, there may be no significant findings on the routine sequnces
due to the lack of sensitivity or the evolution of abnormalities lags behind the ability of the imaging to detect it. In
addition, findings on T1 and T2-weighted imaging of several inborn errors of metabolism may be non-specific and
be seen in other non-genetic conditions. Therefore, additional neuroimaging modalities that have been employed
including diffusion tensor imaging (DTI), magnetic resonance spectroscopy, functional MRI (fMRI), functional near
infrared spectroscopy (fNIRS), or positron emission tomography (PET) imaging may further inform underlying
changes in myelination, biochemistry, and functional connectivity. The use of Magnetic Resonance Spectroscopy
in certain disorders may add a level of specificity depending upon the metabolite levels that are abnormal, as
well as provide information about the process of brain injury (i.e., white matter, gray matter, energy deficiency,
toxic buildup or depletion of key metabolites). It is even more challenging to understand how genetic or metabolic
disorders contribute to short and/or long term changes in cognition which represent the downstream effects
of IEMs. In order to image “cognition” or the downstream effects of a metabolic disorder on domains of brain
function, more advanced techniques are required to analyze underlying fiber tracts or alternatively, methods such
as fMRI enable generation of brain activation maps after both task based and resting state conditions. DTI can
be used to look at changes in white matter tracks. Each imaging modality can explore an important aspect of the
anatomy, physiology or biochemisty of the central nervous system. Their properties, pros and cons are discussed

© The Author(s) 2020. Open Access This article is licensed under a Creative Commons Attribution 4.0
International License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted use,
sharing, adaptation, distribution and reproduction in any medium or format, for any purpose, even commercially, as long
as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license,
and indicate if changes were made.

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