Page 142 - Read Online

Page 432 Gropman et al. J Transl Genet Genom 2020;4:429-45 I http://dx.doi.org/10.20517/jtgg.2020.09

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
[17]
networks compared to the controls .
PHENYLKETONURIA
Phenylketonuria (PKU) is perhaps the best studied metabolic condition in terms of MRI imaging. The
underlying neurobiological aspects of PKU include deficits in executive dysfunction. While not completely
understood, it is believe to be related to the often seen myelination abnormalities. DTI studies have
identified restricted diffusivity in individuals with PKU across a number of brain regions, including the
centrum semiovale, posterior-parietal occipital cortex, prefrontal cortex, optic radiation, putamen, and
anterior corpus callosum [18-25] . Gross WM abnormalities seen at autopsy and on T1 and T2-weighted
magnetic resonance images (MRI) have been reported in patients with PKU [26-36] and white matter (WM)
changes are evident by the second decade of life.

Subtle executive function deficits especially in inhibitory control have been reported in patients with
phenylketonuria (PKU), and this is seen despite early dietary restrictions [19,37] . WM alteration was indeed
influenced by life-long metabolic control but the severity score of WM alterations did not correlate with IQ
or Executive function scoring [35,36] .

Maple syrup urine disease (MSUD) is a disorder involving the catabolism of branched-chain amino
acids (BCAA; leucine, isoleucine, and valine) and is caused by deficiency of the branched-chain keto-
acid dehydrogenase enzyme [37,38] . Two types of brain edema have been described in MSUD. Intramyelinic
edema affects the myelinated white matter (cerebellar white matter, dorsal brainstem, cerebral peduncles,
posterior limb of the internal capsule, and peri-rolandic cerebral white matter), thalami, and globus pallidi.
Intramyelinic edema or “MSUD edema” is the more recognizable pattern, described as hyperintense on T2-
weighted images, diffusion weighted imaging (DWI) and hypointense on T1-weighted images. DTI shows
alterations in both ADC and fractional anisotropy (FA) values [39-42] . Intramyelinic edema which is believed
to be a consequence of energy failure leads to the accumulation of water molecules that intercalate between
the myelinic lamellae resulting in the splitting of the myelin layers. This can be detected by DTI (decreased
FA values) [41,42] . The end result of this process may be delayed myelination and white matter atrophy with
the aforementioned cognitive sequelae.

METHYLMALONIC ACIDEMIA
DWI has been used to investigate ADC in methylmalonic acidemia (MMA). It has been reported to be
associated with restricted water diffusion in the globus pallidus that may resolve after clinical interventions
including carnitine supplementation. Findings from 12 MMA patients demonstrated significant reductions
in FA in the globus pallidus, frontal, temporal and occipital white matter using DTI and we’re not
[43]
appreciated on conventional T1/T2 images . This suggests that, in addition to restricted water diffusion
in the globus pallidus, MMA is associated with more widespread disturbances in white matter integrity.
This is an example of how DTI proved superior to routine imaging in identifying these diffuse lesions.
Neurocognitive lesions in MMA have yet to be investigated with fMRI.

NIEMANN-PICK DISEASE, TYPE C1
Niemann-Pick disease, type C1 (NPC1), is a rapidly progressive neurodegenerative disorder characterized
by cholesterol sequestration within late endosomes and lysosomes. There are no specific or reliable imaging
markers that can be used for management and prognostication. Cerebellar volume deficits are found to
correlate with disease severity. Diffusion tensor imaging (DTI) of the corpus callosum and brainstem, has