title: Elevated dimethylglycine in blood of children with congenital heart defects and their mothers.
abstract: OBJECTIVE
  Congenital Heart Defects (CHD) may be related to nutritional deficiencies affecting the methylation cycle. We aimed to study the metabolic markers of the betaine homocysteine methyl transferase (BHMT) pathway in children with CHD and their mothers compared to children without CHD and their mothers.
  
  
  METHODS
  Children with CHD (n=105, age < 3 years) and mothers of 80 of the affected children were studied. The controls were non-CHDs children of comparable age as the CHD group (n=52) and their mothers (n=50). We measured serum or plasma concentrations of the metabolites of the methylation cycle homocysteine (HCY), methylmalonic acid (MMA), cystathionine, S-adenosylmethionine (SAM), S-adenosylhomocysteine (SAH), betaine, choline, and dimethylglycine (DMG).
  
  
  RESULTS
  Children with CHD had higher plasma SAM (131 vs. 100 nmol/L) and DMG (8.7 vs. 6.0 μmol/L) and lower betaine/DMG ratio (7.5 vs. 10.2) compared to the controls. Mothers of CHD children showed also higher DMG (6.1 vs. 4.1 µmol/L) and lower betaine/DMG ratio compared with the mothers of the controls. Higher SAM levels were related to higher cystathionine, MMA, betaine, choline, and DMG. MMA elevation in the patients was related to higher HCY, SAM, betaine and DMG.
  
  
  CONCLUSIONS
  Elevated DMG in CHD children and their mothers compared to the controls can indicate upregulation of the BHMT pathway in this disease group. Nutritional factors are related to metabolic imbalance during pregnancy that may be related to worse birth outcome.
authors.affiliation: Damascus University, Faculty of Pharmacy, Department of Biochemistry, Damascus, Syria. ranwasyd@gmail.com
authors.forename: Ranwa
authors.initials: R
authors.lastname: Alsayed
authors.forename: Faizeh
authors.initials: F
authors.lastname: Al Quobaili
authors.forename: Samir
authors.initials: S
authors.lastname: Srour
authors.forename: Jürgen
authors.initials: J
authors.lastname: Geisel
authors.forename: Rima
authors.initials: R
authors.lastname: Obeid
mesh_terms: D000328:Adult; D001622:Betaine / Q000378:metabolism; D050940:Betaine-Homocysteine S-Methyltransferase / Q000378:metabolism; D015415:Biomarkers; D002675:Child, Preschool; D002794:Choline / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D005260:Female; D006330:Heart Defects, Congenital / Q000097:blood* / Q000473:pathology; D006801:Humans; D007223:Infant; D008297:Male; D013058:Mass Spectrometry; D009035:Mothers; D012521:Sarcosine / Q000031:analogs & derivatives* / Q000097:blood; D012959:Socioeconomic Factors; D013593:Syria; D014806:Vitamin B 12 Deficiency / Q000378:metabolism
chemical_list: D015415:Biomarkers; D001622:Betaine; C025138:dimethylglycine; D050940:Betaine-Homocysteine S-Methyltransferase; D002794:Choline; D012521:Sarcosine
keywords: BHMT; Betaine; CBS; CHD; Congenital heart defects; DMG; Dimethylglycine; HCY; MMA; Methylation; S-adenosylhomocysteine. MAT, L-methionine S-adenosyltransferase; S-adenosylmethionine; SAH; SAM; UPLC-MS/MS; betaine homocysteine methyl transferase; congenital heart defects; cystathionine beta synthase; dimethylglycine; homocysteine; methylmalonic acid; ultra performance liquid chromatography