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One carbon metabolism disturbances and the C677T MTHFR gene polymorphism in children with autism spectrum disorders.

Paşca SP, Dronca E, Kaucsár T, Craciun EC, Endreffy E, Ferencz BK, Iftene F, Benga I, Cornean R, Banerjee R, Dronca M - J. Cell. Mol. Med. (2009)

Bottom Line: Only in the AD group, plasma cysteine (P= 0.02) and total blood glutathione (P= 0.02) were found to be reduced.Although there was a trend towards lower levels of serine, glycine, N, N-dimethylglycine in AD patients, the plasma levels of these metabolites as well as the levels of homocysteine and cystathionine were not statistically different in any of the ASDs groups.Our study indicates a possible role for the alterations in one carbon metabolism in the pathophysiology of ASDs and provides, for the first time, preliminary evidence for metabolic and genetic differences between clinical subtypes of ASDs.

View Article: PubMed Central - PubMed

Affiliation: Department of Medical Biochemistry, Faculty of Medicine, Iuliu HaTieganu University of Medicine and Pharmacy, Cluj-Napoca, Romania.

ABSTRACT
Autism spectrum disorders (ASDs), which include the prototypic autistic disorder (AD), Asperger's syndrome (AS) and pervasive developmental disorders not otherwise specified (PDD-NOS), are complex neurodevelopmental conditions of unknown aetiology. The current study investigated the metabolites in the methionine cycle, the transsulphuration pathway, folate, vitamin B(12) and the C677T polymorphism of the MTHFR gene in three groups of children diagnosed with AD (n= 15), AS (n= 5) and PDD-NOS (n= 19) and their age- and sex-matched controls (n= 25). No metabolic disturbances were seen in the AS patients, while in the AD and PDD-NOS groups, lower plasma levels of methionine (P= 0.01 and P= 0.03, respectively) and alpha-aminobutyrate were observed (P= 0.01 and P= 0.001, respectively). Only in the AD group, plasma cysteine (P= 0.02) and total blood glutathione (P= 0.02) were found to be reduced. Although there was a trend towards lower levels of serine, glycine, N, N-dimethylglycine in AD patients, the plasma levels of these metabolites as well as the levels of homocysteine and cystathionine were not statistically different in any of the ASDs groups. The serum levels of vitamin B(12) and folate were in the normal range. The results of the MTHFR gene analysis showed a normal distribution of the C677T polymorphism in children with ASDs, but the frequency of the 677T allele was slightly more prevalent in AD patients. Our study indicates a possible role for the alterations in one carbon metabolism in the pathophysiology of ASDs and provides, for the first time, preliminary evidence for metabolic and genetic differences between clinical subtypes of ASDs.

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Related in: MedlinePlus

Levels of methionine, homocysteine, cysteine, total glutathione and α-aminobutyrate in children with AD (A) and PDD-NOS (B) compared to controls.
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fig02: Levels of methionine, homocysteine, cysteine, total glutathione and α-aminobutyrate in children with AD (A) and PDD-NOS (B) compared to controls.

Mentions: The results from metabolite measurements in plasma and serum are listed in Table 1 and graphically represented in Fig. 2. In both the AD and PDD-NOS groups plasma levels of methionine (20.69 ± 1.87 μM versus 27.49 ± 2.01 μM, P= 0.01, Cohen’s d= 0.91, and 23.62 ± 1.09 μM versus 27.51 ± 1.27 μM, P= 0.03, Cohen’s d= 0.69, respectively) and α-aminobutyric acid (11.14 ± 1.17 μM versus 15.73 ± 1.37 μM, P= 0.01 and 10.73 ± 0.83 μM versus 14.62 ± 0.74 μM, P= 0.001, respectively) were lower than in their age- and sex-matched controls, whereas plasma total homocysteine was in the normal range. It is worth noting that the decrease in methionine levels observed in AD was more severe than in PDD-NOS patients (∼25% decrease versus∼14% decrease). Only in the AD group, plasma cysteine levels (181.06 ± 6.42 μM versus 204.76 ± 7.16 μM, P= 0.02; Cohen’s d= 0.91) and total blood glutathione (161.16 ± 10.68 μM versus 242.67 ± 32.94 μM, P= 0.02; Cohen’s d= 0.89) were found to be lower. In contrast, the plasma levels of other amino acids, such as cystathionine, serine, glycine, N-methylglycine and N, N-dimethylglycine did not differ significantly from those of normal controls in any of the ASD groups, although there was a trend towards lower levels of serine, glycine and N, N-dimethylglycine in the AD patients (Table 1). The levels of serum vitamin B12 were in the normal range of values in all ASDs groups; only 3 children with AD had levels below 250 pg/ml, but all subjects with a PDD-NOS diagnosis had levels above this suboptimal value. Serum folate levels were also in the normal range, except for mildly higher levels in AS which reached a borderline statistical significance (13.51 ± 2.06 ng/ml versus 8.17 ± 0.91 ng/ml, P= 0.06). However, in the context of the small group size, this apparent difference in B12 levels needs to be treated with caution.


One carbon metabolism disturbances and the C677T MTHFR gene polymorphism in children with autism spectrum disorders.

Paşca SP, Dronca E, Kaucsár T, Craciun EC, Endreffy E, Ferencz BK, Iftene F, Benga I, Cornean R, Banerjee R, Dronca M - J. Cell. Mol. Med. (2009)

Levels of methionine, homocysteine, cysteine, total glutathione and α-aminobutyrate in children with AD (A) and PDD-NOS (B) compared to controls.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4496129&req=5

fig02: Levels of methionine, homocysteine, cysteine, total glutathione and α-aminobutyrate in children with AD (A) and PDD-NOS (B) compared to controls.
Mentions: The results from metabolite measurements in plasma and serum are listed in Table 1 and graphically represented in Fig. 2. In both the AD and PDD-NOS groups plasma levels of methionine (20.69 ± 1.87 μM versus 27.49 ± 2.01 μM, P= 0.01, Cohen’s d= 0.91, and 23.62 ± 1.09 μM versus 27.51 ± 1.27 μM, P= 0.03, Cohen’s d= 0.69, respectively) and α-aminobutyric acid (11.14 ± 1.17 μM versus 15.73 ± 1.37 μM, P= 0.01 and 10.73 ± 0.83 μM versus 14.62 ± 0.74 μM, P= 0.001, respectively) were lower than in their age- and sex-matched controls, whereas plasma total homocysteine was in the normal range. It is worth noting that the decrease in methionine levels observed in AD was more severe than in PDD-NOS patients (∼25% decrease versus∼14% decrease). Only in the AD group, plasma cysteine levels (181.06 ± 6.42 μM versus 204.76 ± 7.16 μM, P= 0.02; Cohen’s d= 0.91) and total blood glutathione (161.16 ± 10.68 μM versus 242.67 ± 32.94 μM, P= 0.02; Cohen’s d= 0.89) were found to be lower. In contrast, the plasma levels of other amino acids, such as cystathionine, serine, glycine, N-methylglycine and N, N-dimethylglycine did not differ significantly from those of normal controls in any of the ASD groups, although there was a trend towards lower levels of serine, glycine and N, N-dimethylglycine in the AD patients (Table 1). The levels of serum vitamin B12 were in the normal range of values in all ASDs groups; only 3 children with AD had levels below 250 pg/ml, but all subjects with a PDD-NOS diagnosis had levels above this suboptimal value. Serum folate levels were also in the normal range, except for mildly higher levels in AS which reached a borderline statistical significance (13.51 ± 2.06 ng/ml versus 8.17 ± 0.91 ng/ml, P= 0.06). However, in the context of the small group size, this apparent difference in B12 levels needs to be treated with caution.

Bottom Line: Only in the AD group, plasma cysteine (P= 0.02) and total blood glutathione (P= 0.02) were found to be reduced.Although there was a trend towards lower levels of serine, glycine, N, N-dimethylglycine in AD patients, the plasma levels of these metabolites as well as the levels of homocysteine and cystathionine were not statistically different in any of the ASDs groups.Our study indicates a possible role for the alterations in one carbon metabolism in the pathophysiology of ASDs and provides, for the first time, preliminary evidence for metabolic and genetic differences between clinical subtypes of ASDs.

View Article: PubMed Central - PubMed

Affiliation: Department of Medical Biochemistry, Faculty of Medicine, Iuliu HaTieganu University of Medicine and Pharmacy, Cluj-Napoca, Romania.

ABSTRACT
Autism spectrum disorders (ASDs), which include the prototypic autistic disorder (AD), Asperger's syndrome (AS) and pervasive developmental disorders not otherwise specified (PDD-NOS), are complex neurodevelopmental conditions of unknown aetiology. The current study investigated the metabolites in the methionine cycle, the transsulphuration pathway, folate, vitamin B(12) and the C677T polymorphism of the MTHFR gene in three groups of children diagnosed with AD (n= 15), AS (n= 5) and PDD-NOS (n= 19) and their age- and sex-matched controls (n= 25). No metabolic disturbances were seen in the AS patients, while in the AD and PDD-NOS groups, lower plasma levels of methionine (P= 0.01 and P= 0.03, respectively) and alpha-aminobutyrate were observed (P= 0.01 and P= 0.001, respectively). Only in the AD group, plasma cysteine (P= 0.02) and total blood glutathione (P= 0.02) were found to be reduced. Although there was a trend towards lower levels of serine, glycine, N, N-dimethylglycine in AD patients, the plasma levels of these metabolites as well as the levels of homocysteine and cystathionine were not statistically different in any of the ASDs groups. The serum levels of vitamin B(12) and folate were in the normal range. The results of the MTHFR gene analysis showed a normal distribution of the C677T polymorphism in children with ASDs, but the frequency of the 677T allele was slightly more prevalent in AD patients. Our study indicates a possible role for the alterations in one carbon metabolism in the pathophysiology of ASDs and provides, for the first time, preliminary evidence for metabolic and genetic differences between clinical subtypes of ASDs.

Show MeSH
Related in: MedlinePlus