[H-1] Magnetic Resonance Spectroscopy of Urine: Diagnosis of a Guanidinoacetate Methyl Transferase Deficiency Case

Contains fulltext : 87409.pdf (publisher's version ) (Closed access)For the first time, the use of urine [(1)H] magnetic resonance spectroscopy has allowed the detection of 1 case of guanidinoacetate methyl transferase in a database sample of 1500 pediatric patients with a diagnosis of central nervous system impairment of unknown origin. The urine [(1)H] magnetic resonance spectroscopy of a 9-year-old child, having severe epilepsy and nonprogressive mental and motor retardation with no apparent cause, revealed a possible guanidinoacetic acid increase. The definitive assignment of guanidinoacetic acid was checked by addition of pure substance to the urine sample and by measuring [(1)H]-[(1)H] correlation spectroscopy. Diagnosis of guanidinoacetate methyl transferase deficiency was further confirmed by liquid chromatography-mass spectrometry, brain [(1)H] magnetic resonance spectroscopy, and mutational analysis of the guanidinoacetate methyl transferase gene. The replacement therapy was promptly started and, after 1 year, the child was seizure free. We conclude that for this case, urine [(1)H] magnetic resonance spectroscopy screening was able to diagnose guanidinoacetate methyl transferase deficiency.1 januari 201

Relationship between plasma F₂-IsoPs and Xq28 size (univariate regression analysis).

<p>A positive linear relationship of plasma F₂-IsoPs vs. Xq28 duplication/triplication size is showed. The strength of the relationship is indicated by the correlation coefficient (r = 0.9181, P = 0.0098). The linear regression equation was reported.</p

Oxidative stress marker plasma levels in MDS and RTT.

<p>Levels of NPBI, plasma free F₂-IsoPs, F₄-NeuroPs, and F₂-dihomo-IsoPs in MDS are compared with those of RTT and healthy control subjects. All the statistical significant differences were reported. Legend: ANOVA, analysis of variance; F₂-dihomo-isoPs, F₂-dihomo-isoprostanes; F₂-IsoPs, F₂-isoprostanes; F₄-NeuroPs, F₄-neuroprostanes; IE-NPBI, intraerythrocyte non protein bound iron; MDS, <i>MECP2</i> Duplication Syndrome; p-NPBI, plasma non protein bound; RTT, Rett syndrome.</p

Graphical view of the <i>MECP2</i> duplications/triplication.

<p>Graphical view of the <i>MECP2</i> duplications/triplication was created with custom tracks in the UCSC genome browser (GRCh37/hg19), (Patient 1 was identified with a triplication). The involved regions are shown in blue and <i>MECP2</i> is marked by a red circle.</p

Commonalities and differences between <i>MECP2</i> duplication syndrome and Rett syndrome.

<p>Commonalities and differences between <i>MECP2</i> duplication syndrome and Rett syndrome.</p

Routine chemistry biomarkers in patients with <i>MECP2</i> duplication syndrome, Rett syndrome, and control subjects.

<p>Routine chemistry biomarkers in patients with <i>MECP2</i> duplication syndrome, Rett syndrome, and control subjects.</p

<i>MECP2</i> duplication syndrome: clinical features and genetic details.

<p><i>MECP2</i> duplication syndrome: clinical features and genetic details.</p

MECP2 duplication syndrome: Evidence of enhanced oxidative stress. A comparison with Rett syndrome

Rett syndrome (RTT) and MECP2 duplication syndrome (MDS) are neurodevelopmental disorders caused by alterations in the methyl-CpG binding protein 2 (MECP2) gene expression. A relationship between MECP2 loss-of-function mutations and oxidative stress has been previously documented in RTT patients and murine models. To date, no data on oxidative stress have been reported for the MECP2 gain-of-function mutations in patients with MDS. In the present work, the pro-oxidant status and oxidative fatty acid damage in MDS was investigated (subjects n = 6) and compared to RTT (subjects n = 24) and healthy condition (subjects n = 12). Patients with MECP2 gain-of-function mutations showed increased oxidative stress marker levels (plasma non-protein bound iron, intraerythrocyte non-protein bound iron, F2-isoprostanes, and F4-neuroprostanes), as compared to healthy controls (P ≤ 0.05). Such increases were similar to those observed in RTT patients except for higher plasma F2-isoprostanes levels (P < 0.0196). Moreover, plasma levels of F2-isoprostanes were significantly correlated (P = 0.0098) with the size of the amplified region. The present work shows unique data in patients affected by MDS. For the first time MECP2 gain-of-function mutations are indicated to be linked to an oxidative damage and related clinical symptoms overlapping with those of MECP2 loss-of-function mutations. A finely tuned balance of MECP2 expression appears to be critical to oxidative stress homeostasis, thus shedding light on the relevance of the redox balance in the central nervous system integrity