L’acidurie L2-hydroxyglutarique

L’acidurie L2-hydroxyglutarique

Il s’agit d’une maladie métabolique neurodégénérative autosomique récessive liée à une accumulation et à une élévation d’acide L-2-hydroxyglutarique retrouvés dans le plasma sanguin, les urines et le liquide céphalo-rachidien.

Le gène responsable de l’acidurie L-2-hydroxyglutarique a été identifié sur le chromosome 14q22.1 (1).

Sa détection se fait à l’aide de la chromatographie en phase gazeuse et de la spectrométrie de masse qui mettent en évidence des acides organiques de type hydroxyglutarique

Les enfants atteints présentent, vers l’âge de deux ans, un retard psychomoteur modéré, une ataxie progressive, des signes extrapyramidaux associés à une baisse progressive du quotient intellectuel.

En IRM, il existe une atteinte de la substance blanche multifocale ou diffuse avec prédilection pour la substance blanche sous corticale frontale (3) avec dans une moindre mesure une atteinte de la substance blanche profonde qui apparaît en hypersignal T2 et hyposignal T1(2).

La substance blanche périventriculaire est habituellement  respectée.
Elle s’accompagne d’une atrophie diffuse sous la forme d’un élargissement des espaces veineux périvasculaires, du système ventriculaire, des sillons corticaux à prédominance frontale et parfois d’une atteinte cérébelleuse(3).

Les globi pallidi sont en hypersignal T2 et isosignal T1 alors que les noyaux dentelés sont en hypersignal T2 et hyposignal T1. Ces derniers sont parfois respectés (4)

Il existe aussi un discret hypersignal T2 des putamen et parfois de la tête des noyaux caudés. Le corps calleux peut être atrophié (3) mais sans anomalie de signal alors que le tronc cérébral et la substance blanche cérébelleuse sont habituellement normaux (2)

 

Deux formes ont été décrites par D’incerti (2); la première de début très précoce avec atteinte de la substance blanche multifocale sous corticale et atteinte marquée des NGC avec macrocéphalie et une deuxième de début plus tardif où l’atteinte de la substance blanche est plus diffuse avec moindre atteinte des NGC sans macrocéphalie.

 

Il existe de multiples diagnostics différentiels.

La maladie de CANAVAN: donne, elle aussi, une atteinte de la substance blanche à prédominance sous corticale avec atteinte des noyaux gris centraux et des noyaux dentelés. Elle se caractérise par une substance blanche oedémateuse hypersignalT2 qui prédomine dans la substance blanche sous corticale et qui affecte le tronc cérébral avec hypersignal T2 des Globi pallidi, des noyaux dentelés et parfois des noyaux antéro-lateraux des thalami. La SRM peut montrer une élévation du NAA dans la substance blanche.

Deux éléments permettent d’aider à la différenciation : l’atteinte du tronc cérébral (5) et l’élévation du NAA dans la substance blanche en SRM sont en faveur de la maladie de CANAVAN (6).
La maladie de KEARNS-SAYRE présente une atteinte sous corticale moins marquée (2).
Les maladies mitochondriales (LEIGH par exemple) qui peuvent aussi donner une atteinte striatale mais avec des hypersignaux bien plus marqués.

 

La leucodystrophie métachromatique se caractérise par une atteinte de la substance blanche respectant les fibres sous corticales et les noyaux gris centraux.

 

La maladie d’ALEXANDER se caractérise en IRM par une atteinte bilatérale et symétrique des fibres en U de la région frontale chez un patient macrocéphale

 

MEMO

L’acidurie L-2-hydroxyglutarique est une maladie neurodégénérative rare qui peut se traduire par un tableau neurologique relativement frustre, comportant difficultés scolaires et signes cérébelleux très discrets; l’épilesie est plus tardive. L’atteinte de la substance blanche frontale sous corticale, des noyaux lenticulaires et des noyaux dentelés est caractéristique et orientera le diagnostic.

 

BIBLIOGRAPHIE

1-L-2-Hydroxyglutaric aciduria: clinical, genetic, and brain MRI characteristics in

two adult sisters. Eur J Neurol. 2006 May;13(5):499-504.

Goffette SM, Duprez TP, Nassogne MC, Vincent MF, Jakobs C, Sindic CJ.

 

2-L-2-Hydroxyglutaric aciduria: MRI in seven cases.
Neuroradiology. 1998 Nov;40(11):727-33.

D’Incerti L, Farina L, Moroni I, Uziel G, Savoiardo M.

 

3-L-2-Hydroxyglutaric aciduria: clinical, biochemical and magnetic resonance

imaging in six Portuguese pediatric patients.Brain Dev. 1997 Jun;19(4):268-73.

Barbot C et coll

 

4-L-2-hydroxyglutaric aciduria: clinical, neuroimaging, and neuropathological

findings.Arch Neurol. 2005 Apr;62(4):666-70.

Seijo-Martínez M, Navarro C, Castro del Río M, Vila O, Puig M, Ribes A, Butron M.

 

5-Clinical and magnetic resonance imaging features of L-2-hydroxyglutaric acidemia:

report of three cases in comparison with Canavan disease.
J Child Neurol. 1996 Sep;11(5):373-7

Topçu M, et coll

 

6-A. James Barkovich (ed): Pediatric neuroimaging, 4th edn: Lippincott Williams and Wilkins, 2005. 976 pages,

 

 

 

 

 

 

 

 

 

 

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