Differential expression of cystathionine beta synthase in adolescents with Down syndrome: impact on adiposity.

Purpose: Obesity is more prevalent among people with Down Syndrome (DS) compared to general population. In this pilot study, we investigated the effect of cystathionine beta-synthase (CBS) overdosage on the regulation of transsulfuration pathway and the obesity phenotype in fifty adolescents (25 obese/overweight and 25 lean) with trisomy 21. Methods: The transcriptional levels of CBS in leukocytes and its translational levels in plasma were quantified using real time polymerase chain reaction and enzyme-linked immunosorbent assay respectively. Meanwhile, ultra performance liquid chromatography tandem mass spectrometry was used to determine the plasma concentrations of methionine, homocysteine, cystathionine and cysteine. Fasting plasma lipid profiles were assessed by colorimetric assays. The anthropometric measurements and indices of all subjects were recorded. Results: Both DS groups had comparable levels of CBS transcripts (p = 0.2734). The plasma levels of the enzyme were significantly higher in the lean DS cases (p = 0.0174) compared to the obese/overweight participants. Total cholesterol, triglycerides, high-density lipoprotein, low-density lipoprotein, methionine, homocysteine, cystathionine and cysteine showed similar plasma levels in both groups. However, the plasma cysteine levels exceeded the normal range in all DS cases. We reported a statistically significant inverse association between CBS enzyme levels and weight (r= - 0.3498, p = 0.0128), hip circumference (r= - 0.3584, p = 0.0106), body mass index (r= - 0.3719, p = 0.0078) and body adiposity index (r= - 0.3183, p = 0.0243). Conclusions: Our data suggests that the high concentrations of CBS enzyme together with cysteine modulate the DS obesity presumably through increased hydrogen sulfide production which has recently showed anti-adiposity effects.

Prenatal diagnosis of mucopolysaccharidoses type II by two-dimensional electrophoresis and mass spectrometry in amniotic fluid.

AIM: To introduce a quantitative determination of heparan sulfate and dermatan sulfate by mass spectrometry and to compare it with two-dimensional electrophoresis of the glycosaminoglycans in the amniotic fluid for the prenatal diagnosis of mucopolysaccharidoses type II (MPS II). METHODS: Thirty pregnancies each with single fetus were subjected to amniocentesis at 16 weeks: 10 with a previously affected MPS II infant and 20 as controls. Prenatal diagnosis was done by both mass spectrometry two two-dimensional electrophoresis. RESULTS: Two-dimensional electrophoresis showed four affected with MPS II and six unaffected fetuses. Mass spectrometry verified these results. CONCLUSION: Two-dimensional electrophoresis of the glycosaminoglycans in amniotic fluid is a good qualitative method and mass spectrometry is a new accurate quantitative method for prenatal diagnosis of MPS II. Quantitative determination of glycosaminoglycans in amniotic fluid by mass spectrometry is both rapid and accurate. Prenatal diagnosis is recommended for at risk pregnancies and mass spectrometry offers speed and quantitation.

Association between biomarkers of vitamin B12 status and the risk of neural tube defects.

AIM: The aim of this study was to evaluate the association between vitamin B12 and its biomarkers and the risk of neural tube defects. METHODS: A total of 120 pregnant Egyptian women were included in the study. They were classified into two groups. Group A consisted of 50 women with neural tube defects in current pregnancy or with a history in previous pregnancies, and Group B consisted of 70 women with no history of neural tube defects in previous pregnancies or in the current pregnancy. All women were subjected to ultrasound anomaly scan and serum analysis of vitamin B12, homocysteine (Hcy), methyl malonic acid (MMA) and active vitamin B12 concentrations. Receiver operating characteristic curve analysis was used to determine the best cut-off values of vitamin B12. RESULTS: Serum levels of vitamin B12 were decreased in Neural tube defects (NTDs) cases compared to controls (2.736 vs 3.091 ng/mL; P = 0.0015), while Hcy and MMA concentrations were elevated (18.39 vs 13.95 µmol/L; P = 0.0008 and 263 vs 229.7 µmol/L; P = 0.003, respectively). Active vitamin B12 reduction was not statistically significant (96.8 vs 99.36 pmol/L; P = 0.8013). The optimal cut-off value of vitamin B12, 2.9 ng/mL, is the best threshold to expect neural tube defects, with a sensitivity of 60% and specificity of 74.29%. CONCLUSION: Low vitamin B12 is a risk factor for having a fetus with neural tube defects. The monitoring of MMA and Hcy levels might be important in understanding and following cases with neural tube defects. Adding vitamin B12 to folic acid may help to decrease the incidence of neural tube defects in the Egyptian population.

Role of polyunsaturated fatty acids in the management of Egyptian children with autism.

OBJECTIVE: Estimation of free polyunsaturated fatty acids (PUFAs) in blood and evaluation of behavior of autistic children before and after taking fish oil (Efalex) were performed. DESIGN AND METHODS: 30 autistic children (18 males and 12 females) aged 3-11 years and 30 healthy children as control group were included in this study. Tandem mass spectrometry and CARS were used to estimate the free PUFAs from dried blood spot and to evaluate the autistic behavior respectively. RESULTS: Before taking Efalex, linolenic acid showed a significant reduction (71%), followed by docosahexaenoic acid (65%) and arachidonic acid (45%), while linoleic acid was the least affected PUFA (32%). After taking Efalex, 66% of autistic children showed clinical and biochemical improvement, linolenic acid and docosahexaenoic acid showed the highest levels after Efalex supplementation. CONCLUSION: PUFA supplementation may play an important role in ameliorating the autistic behavior.