Methylation capacity in children with severe cerebral palsy

Abstract

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). 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. 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. 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.