Levels of 5-methyltetrahydrofolate and ascorbic acid in cerebrospinal fluid are correlated: Implications for the accelerated degradation of folate by reactive oxygen species

Aylett, Sophie-Beth; Neergheen, Viruna; Hargreaves, Iain P.; Eaton, Simon; Land, John M.; Rahman, Shamima; Heales, Simon

doi:10.1016/j.neuint.2013.10.002

Cited by 19 publications

(24 citation statements)

References 24 publications

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“…Such methods are not generally available in a diagnostic setting. For the diagnosis of CFD, the most frequently used method is high performance liquid chromatography (HPLC) with fluorescence detection or electrochemical detection (ECD) of 5‐MTHF in CSF . Most methods rely on the separation of 5‐MTHF on a C18 HPLC column followed by ECD or fluorescence detection.…”

Section: Analytical Methods For Assessment Of Folate Statusmentioning

confidence: 99%

“…However, we have noted that 5‐MTHF may degrade quickly in occasional CSF samples. The reason for this is not clear but could be related to oxidative catabolism due to deficiency of antioxidants such as ascorbic acid and/or increased generation of reactive oxygen species . Consequently, we recommend that all CSF samples for 5‐MTHF analysis should be snap frozen and stored at −70°C.…”

Section: Analytical Methods For Assessment Of Folate Statusmentioning

confidence: 99%

“…There appears to be no rostro‐caudal gradient for CSF 5‐MTHF but CSF 5‐MTHF concentrations are age‐related with CSF 5‐MTHF typically decreasing with age . Most laboratories have their own age‐related reference ranges with broad agreement between different laboratories . Reference ranges can vary between laboratories in different countries, possibly owing to differences in “control” groups and other factors such as dietary differences.…”

Section: Analytical Methods For Assessment Of Folate Statusmentioning

confidence: 99%

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Cerebral folate deficiency: Analytical tests and differential diagnosis

Pope

Artuch

Heales

et al. 2019

J of Inher Metab Disea

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Cerebral folate deficiency is typically defined as a deficiency of the major folate species 5‐methyltetrahydrofolate in the cerebrospinal fluid (CSF) in the presence of normal peripheral total folate levels. However, it should be noted that cerebral folate deficiency is also often used to describe conditions where CSF 5‐MTHF is low, in the presence of low or undefined peripheral folate levels. Known defects of folate transport are deficiency of the proton coupled folate transporter, associated with systemic as well as cerebral folate deficiency, and deficiency of the folate receptor alpha, leading to an isolated cerebral folate deficiency associated with intractable seizures, developmental delay and/or regression, progressive ataxia and choreoathetoid movement disorders. Inborn errors of folate metabolism include deficiencies of the enzymes methylenetetrahydrofolate reductase, dihydrofolate reductase and 5,10‐methenyltetrahydrofolate synthetase. Cerebral folate deficiency is potentially a treatable condition and so prompt recognition of these inborn errors and initiation of appropriate therapy is of paramount importance. Secondary cerebral folate deficiency may be observed in other inherited metabolic diseases, including disorders of the mitochondrial oxidative phosphorylation system, serine deficiency, and pyridoxine dependent epilepsy. Other secondary causes of cerebral folate deficiency include the effects of drugs, immune response activation, toxic insults and oxidative stress. This review describes the absorption, transport and metabolism of folate within the body; analytical methods to measure folate species in blood, plasma and CSF; inherited and acquired causes of cerebral folate deficiency; and possible treatment options in those patients found to have cerebral folate deficiency.

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Section: Analytical Methods For Assessment Of Folate Statusmentioning

confidence: 99%

Section: Analytical Methods For Assessment Of Folate Statusmentioning

confidence: 99%

Section: Analytical Methods For Assessment Of Folate Statusmentioning

confidence: 99%

See 1 more Smart Citation

Cerebral folate deficiency: Analytical tests and differential diagnosis

Pope

Artuch

Heales

et al. 2019

J of Inher Metab Disea

Self Cite

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“…Therefore, it is possible that other mechanisms, beyond just an energy-deficiency state, are a contributing factor to CFD. Recently, oxidative stress was proposed as a mechanism for CFD [38] associated with mitochondrial disorders. Loss of respiratory chain activity can result in increased generation of mitochondrial reactive oxygen species, leading to accelerated catabolism of 5-MTHF.…”

Section: Cerebral Folate Deficiency and Mitochondrial Disordersmentioning

confidence: 99%

“…Loss of respiratory chain activity can result in increased generation of mitochondrial reactive oxygen species, leading to accelerated catabolism of 5-MTHF. Prevention of such catabolism, in vitro, by ascorbic acid raises the possibility of an adjunct to the folate replacement, in the form of folinic acid, to treat the CFD [38].…”

Section: Cerebral Folate Deficiency and Mitochondrial Disordersmentioning

confidence: 99%