L-2-hydroxyglutaric aciduria

Case contributed by Dr Yune Kwong


A patient with a known neurometabolic disorder presents with deteriorating ataxia and behavioural difficulties

Patient Data

Age: 16
Gender: Male

There is bilateral and symmetrical high signal of the white matter involving the subcortical U fibers. The deep white matter of the periventricular region and corpus callosum are preserved. The basal ganglia are of high signal, but the thalamus and brainstem are not affected. Marked signal change in the dentate nuclei is seen. 

The areas of high T2/FLAIR intensity are of high signal on DWI (B=1000), but on subsequent ADC map this is shown to be due to T2 shine-through.

On ADC map, the regions of high T2/FLAIR intensity are shown to have increased diffusivity.

Case Discussion

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In this case, the patient had known L-2-Hydroxyglutaric aciduria prior to imaging. His parents are first-degree cousins, and this is consistent with the autosomal recessive inheritance. Definitive diagnosis was previously performed by identifying L-2-Hydroxyglutaric aciduria in urine, where it is usually massive raised. However, MRI has characteristic findings and can often enable diagnosis prior to biochemical investigations. The signal changes start multi-focally in the U-fibers before progressing to confluency. This centripetal pattern of involvement is seen in only a few other leukodystrophies (Canavan and Kearns-Sayre syndrome), and the further lack of involvement of the brainstem helps to narrow the differential to L-2-Hydroxyglutaric aciduria .

In our case, the patient still has reasonable function at age 16, being self-ambulatory with mild learning difficulties. This is typical of L-2-Hydroxyglutaric aciduria, where the onset is insiduous, progression is slow and patients mostly survive into adulthood. This is in contrast to the more fulminant course of other leukodystrophies

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Case information

rID: 20918
Published: 21st Dec 2012
Last edited: 14th Aug 2019
Inclusion in quiz mode: Included

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