Case of the Week
Section Editors: Matylda Machnowska1 and Anvita Pauranik2
1University of Toronto, Toronto, Ontario, Canada
2BC Children's Hospital, University of British Columbia, Vancouver, British Columbia, Canada
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October 20, 2022
L-2 Hydroxyglutaric Aciduria
- Background:
- L-2 hydroxyglutaric aciduria is an organic aciduria with recessive autosomal inheritance (pathogenic mutation on the L2HGDH gene) causing dysfunction of the enzyme L-2-hydroxyglutarate dehydrogenase, leading to accumulation of L-2 hydroxyglutaric acid, which results in neurodegenerative effects.
- Clinical Presentation:
- The disease may have slow clinical progression.
- Most patients display delayed mental and motor development, epilepsy, and cerebellar dysfunction.
- Key Diagnostic Features:
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Brain MRI shows a symmetric T2 and FLAIR high signal intensity and T1 low signal intensity of the subcortical white matter (U-fibers), globus pallidus, and dentate nucleus. White matter involvement presents a centripetal pattern, starting in the U-fibers and extending to the deeper white matter with a confluent pattern as the disease progresses. Even in advanced cases, the corpus callosum, internal capsule, and periventricular white matter are spared. There is no involvement of the brainstem and cerebellar white matter. There is no contrast enhancement and no restricted diffusion. Advanced cases show cerebral and cerebellar vermis atrophy.
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The definite diagnosis is made by urinary organic acid screening with gas chromatography–mass spectrometry and liquid chromatography–tandem mass spectrometry.
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- Differential Diagnoses:
- The differential diagnosis mainly includes Canavan disease and Kearns-Sayre syndrome. Canavan disease usually has bilateral thalamic involvement, restricted diffusion, and increased NAA on proton MR spectroscopy. Kearns-Sayre syndrome has a distinctive clinical triad with ophthalmoplegia, retinal pigmentation, and cardiac conduction defects. Distinctive MRI findings of this syndrome are symmetric thalamic, red nucleus, and brainstem tegmentum involvement, with restricted diffusion.
- Treatment:
- There is currently no treatment; the management is based on symptom control.
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