Methylation capacity in children with severe cerebral palsy.
BACKGROUND
Methylation cycle and folate-mediated one-carbon metabolism maintenance is important for many physiological processes including neurotransmitter regulation, nerve myelination and DNA synthesis. These processes play an indispensible role in growth and development, as well as in cognitive function and neuromuscular stability, which are key issues in children with severe cerebral palsy (CP).


METHODS
Blood samples were collected from children with severe CP (n = 24) and age-matched typically developing healthy controls (n = 24), as an exploratory study. The CP group was divided into orally (O) or enterally fed via percutaneous endoscopic gastrostomy (E). Concentrations of red cell folate (RCF), methylmalonic acid (MMA), mean cell volume (MCV), homocysteine (Hcy), cystathionine, choline, betaine and urate were assayed.


RESULTS
Homocysteine was increased in both O mean (±SD) = 6·28 (±1·81 μM) and E = 6·03 (±1·28), vs. controls = 5·07 (±0·98) P = 0·02. Higher MMA was found in controls = 157 (±54) and O = 141 (±101), vs. E = 88(±21) P = 0·05. RCF was higher in E = 1422 (±70 nM) vs. O = 843 (±80) and controls = 820 (±43) P < 0·001. MCV z-scores were elevated in E = 3·1 (±1·8) and O = 1·1 (±1·1) compared with controls = -0·2 (±1·1) P < 0·001. Urate was significantly reduced in O = -0·64 (±1·38) and E = -0·87 (±0·71), vs. controls = 0·18 (±0·62) P = 0·006.


CONCLUSIONS
Raised MCV in the presence of elevated red cell folate, adequate B12 status and low plasma urate suggest potential methyltetrahydrofolate trapping and impaired purine synthesis. Well-documented malnutrition issues in O may explain differences between CP groups. These data support the hypothesis of possible dysregulation in methylation capacity and/or folate one-carbon metabolism, although more research is needed to elucidate a precise mechanism.
Children's Nutrition Research Centre, School of Medicine, The University of Queensland, Herston, QLD 4029, Australia. n.schoendorfer@uq.edu.au
Niikee C
NC
Schoendorfer
Rima
R
Obeid
Leith
L
Moxon-Lester
Nita
N
Sharp
Luis
L
Vitetta
Roslyn N
RN
Boyd
Peter S W
PS
Davies
D001622:Betaine / Q000378:metabolism; D015415:Biomarkers; D016022:Case-Control Studies; D002547:Cerebral Palsy / Q000097:blood*; D002648:Child; D002675:Child, Preschool; D002794:Choline / Q000378:metabolism; D003540:Cystathionine / Q000378:metabolism; D019175:DNA Methylation; D004909:Erythrocyte Indices; D004910:Erythrocyte Membrane / Q000378:metabolism*; D005492:Folic Acid / Q000378:metabolism*; D005494:Folic Acid Deficiency / Q000097:blood / Q000378:metabolism; D006710:Homocysteine / Q000378:metabolism*; D006801:Humans; D008764:Methylmalonic Acid / Q000378:metabolism*; D011793:Queensland; D012720:Severity of Illness Index; D014527:Uric Acid / Q000378:metabolism*
D015415:Biomarkers; D006710:Homocysteine; D014527:Uric Acid; D003540:Cystathionine; D001622:Betaine; D008764:Methylmalonic Acid; D005492:Folic Acid; D002794:Choline