Paraoxonase 1 activities and polymorphisms in autism spectrum disorders.

Autism spectrum disorders (ASD) comprise a complex and heterogeneous group of conditions of unknown aetiology, characterized by significant disturbances in social, communicative and behavioural functioning. Recent studies suggested a possible implication of the high-density lipoprotein associated esterase/lactonase paraoxonase 1 (PON1) in ASD. In the present study, we aimed at investigating the PON1 status in a group of 50 children with ASD as compared to healthy age and sex matched control participants. We evaluated PON1 bioavailability (i.e. arylesterase activity) and catalytic activity (i.e. paraoxonase activity) in plasma using spectrophotometric methods and the two common polymorphisms in the PON1 coding region (Q192R, L55M) by employing Light Cycler real-time PCR. We found that both PON1 arylesterase and PON1 paraoxonase activities were decreased in autistic patients (respectively, P < 0.001, P < 0.05), but no association with less active variants of the PON1 gene was found. The PON1 phenotype, inferred from the two-dimensional enzyme analysis, had a similar distribution in the ASD group and the control group. In conclusion, both the bioavailability and the catalytic activity of PON1 are impaired in ASD, despite no association with the Q192R and L55M polymorphisms in the PON1 gene and a normal distribution of the PON1 phenotype.

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

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.

Maternal obesity - a risk factor for metabolic syndrome in children.

OBJECTIVE: To determine the association between the metabolic syndrome in children (MS) and the pre-pregnancy nutritional status of the mother. DESIGN AND METHODS: A total number of 180 children aged between 6-19 years were examined. Self reported data about parents and their children were collected. The children underwent physical examination; weight, height, waist circumference, blood pressure (BP) were measured. The nutritional status of the children was assessed by body mass index (BMI) and laboratory tests needed to diagnose MS were performed. IDF criteria for MS were used in children 10 years and older, and age and gender specific cut-off points in children younger than 10 years. The mothers were classified in the normal weight, overweight and obese categories according to the pre-pregnancy BMI. The statistical analysis of the data was descriptive and inferential analysis. In the bivariate analysis of the association between qualitative variables, we used the Chi-Square test and the exact Fisher test. The statistical analysis was performed with SPSS v 13.0. RESULTS: 73 (40.55%) children were normal weight, 54 (30%) were overweight and 53 (29.44%) were obese. None of the normal weight children, 16 (29.60%) of the overweight and 23 (43.40%) of the obese ones had MS; 125 (69.44%) of the mothers were normal weight, 44 (24.44%) were overweight and 11 (6.11%) were obese. Pre-pregnancy maternal BMI was significantly associated with offspring MS in both genders, obese children and in the 10-16 age group. CONCLUSIONS: Pre-pregnancy maternal overweight/obesity represents a risk factor for offspring MS. The results are very difficult to compare between studies because of different cut-off values and definition of MS in children. If prevention is the goal rather than treatment, the perinatal period may be an important focus for future research.