Treatment with Vigabatrin May Mimic α‐Aminoadipic Aciduria

Vallat, C; Rivier, François; Bellet, H.; Bornier, B. Magnan De; Mion, H; Échenne, B.

doi:10.1111/j.1528-1157.1996.tb00655.x

Cited by 22 publications

(7 citation statements)

References 13 publications

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“…This value represents a 24-fold increase compared to the basal AAA values seen at zero time point that was estimated at approximately 3 μM. This value is similar to the 4 μM basal AAA concentration found in normal mouse plasma, as reported in the mouse multiple tissue metabolome database (MMMDB) (Sugimoto et al 2012 ) and in the human metabolome database (HMDB 2.0) (Vallat et al 1996 ; Wishart et al 2013 ) These results suggest that lysine is rapidly oxidized to AAA reaching a maximum within the first 2 h after lysine administration. Four to 6 h following IP lysine injection, AAA returned to concentrations that were not statistically different from that observed for zero time point.…”

Section: Resultssupporting

confidence: 82%

Simultaneous detection of lysine metabolites by a single LC–MS/MS method: monitoring lysine degradation in mouse plasma

et al. 2016

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Detection and quantification of lysine degradation metabolites in plasma is necessary for the diagnosis and follow-up of diseases such as pyridoxine-dependent epilepsy. The principal metabolites involved in the disease are related to the first steps of lysine oxidation, either through the saccharopine or the pipecolate pathways. Currently, there are three different analytical methods used to assess the content of these metabolites in urine and plasma, but they require different sample preparations and analytical equipment. Here, we describe a protocol that calls for a simple sample preparation and uses liquid chromatography tandem mass spectrometry (LC–MS/MS) that allows simultaneous detection and quantification of underivatized l-saccharopine, l-aminoadipic acid, l-pipecolic acid, piperideine-6-carboxylate, l-glutamic acid, and pyridoxal-5-phosphate in plasma samples. To validate the method we analyzed the time course degradation after intraperitoneal injection of l-lysine in C57BL/6/J mice. We observed that the degradation of lysine through the saccharopine pathway reached a maximum within the first 2 h. At this time point there was an increase in the levels of the metabolites saccharopine, aminoadipic acid, and pipecolic acid by 3-, 24- and 3.4-fold, respectively, compared to time zero levels. These metabolites returned to basal levels after 4–6 h. In conclusion, we have developed a LC–MS/MS approach, which allows simultaneous analysis of lysine degradation metabolites without the need for derivatization.Electronic supplementary materialThe online version of this article (doi:10.1186/s40064-016-1809-1) contains supplementary material, which is available to authorized users.

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Section: Resultssupporting

confidence: 82%

Simultaneous detection of lysine metabolites by a single LC–MS/MS method: monitoring lysine degradation in mouse plasma

et al. 2016

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“…37 Furthermore, AAA levels were reported to increase in the plasma and urine of epileptic patients under VGB therapy. 38 AAA is long known to be a gliotoxin that affects Müller glial cells, 39 leading to an upregulation of GFAP and secondarily to photoreceptor dysmorphogenesis. 40 The involvement of AAA gliotoxicity in VGB-induced visual field constriction is further supported by the histological similarities between AAA-treated developing retina 41 and retina of VGB-treated animals.…”

Section: Fig 6 Ultrastructural Alterations Of Photoreceptors and Retmentioning

confidence: 99%

Vigabatrin, the GABA‐transaminase inhibitor, damages cone photoreceptors in rats

Duboc

Hanoteau

Silva

et al. 2004

Annals of Neurology

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Epileptic patients experienced an irreversible loss of their peripheral visual field upon treatment with vigabatrin (gamma-vinyl GABA), an inhibitor of the GABA degrading enzyme, GABA transaminase. Subsequently, central visual function was reported to also be irreversibly altered. This visual loss is associated with a decrease in the electroretinogram measurement localizing the deficit to the retina. To investigate its cellular origin, we treated rats daily with vigabatrin for 45 days. Two days after arresting this treatment, rats exhibited an irreversible decrease in the photopic electroretinogram, the flicker response, and the oscillatory potentials. These functional alterations were associated with a peripheral disorganization of the outer retina. However, photoreceptor damage was not limited to these disorganized areas, but cone inner and outer segments were severely injured in more central areas and their numbers were irreversibly decreased by 17 to 20%. Ultrastructural examination of the retina confirmed the presence of major photoreceptor damages, which were further supported by terminal deoxynucleotidyltransferase-mediated dUTP nick end labeling (TUNEL) and caspase-3 activation both indicative of photoreceptor apoptosis. This study suggests that the visual field loss in vigabatrin-treated epileptic patients may result from a sequence of events starting from cone cell injury to a more severe disorganization of the photoreceptor layer.

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“…In addition, urine amino acid analysis revealed marked excretion of α-aminoadipic acid and β-alanine, indicative of vigabatrin therapy. 103,104 Further inquiry revealed that the patient had indeed received VPA (110mg/day) and vigabatrin (625mg/day) at the time of sampling.…”

mentioning

confidence: 99%

Pitfalls in the diagnosis of glycine encephalopathy (non‐ketotic hyperglycinemia)

Korman

Gutman

2002

Develop Med Child Neuro

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Treatment with Vigabatrin May Mimic α‐Aminoadipic Aciduria

Cited by 22 publications

References 13 publications

Simultaneous detection of lysine metabolites by a single LC–MS/MS method: monitoring lysine degradation in mouse plasma

Simultaneous detection of lysine metabolites by a single LC–MS/MS method: monitoring lysine degradation in mouse plasma

Vigabatrin, the GABA‐transaminase inhibitor, damages cone photoreceptors in rats

Pitfalls in the diagnosis of glycine encephalopathy (non‐ketotic hyperglycinemia)

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