In Cerebral folate deficiency: Analytical tests and differential diagnosis, I came across a tough phrase:
Neurological disease was first linked to folate deficiency by Pincus and co-workers in 1973 (Reynolds et al, 1973) and low CSF folate levels were first reported in 1981 (Botez and Bachevalier 1981). Cerebral folate deficiency was subsequently defined by Raemakers and Blau (2004) as ‘any neurological syndrome associated with a low CSF 5-MTHF, in the presence of normal folate metabolism outside the nervous system.’ However, it should be noted that cerebral folate deficiency is often used to describe conditions where CSF 5-MTHF is low, regardless of the peripheral folate status. A variety of causes of cerebral folate deficiency have been described, ranging from inborn errors of metabolism including metabolic recycling defects (DHFR and MTHFR deficiencies) and disorders of folate transport (e.g. FOLR1 and PCFT defects, and mitochondrial disorders leading to impaired folate transport) to possible over-utilisation/degradation defects such as L-dopa methylation and neurodegeneration. The primary transport and metabolic defects typically present with extremely low cerebrospinal fluid (CSF) concentrations of 5-MTHF below 10 nmol/L prior to treatment.
Do they mean
- excessive utilization of folate and folate-derived compounds, leading to hypermethylation of L-dopa, or
- excessive degradation of folates, leading to neurodegeneration"
Or do they mean "L-dopa methylation and neurodegeneration" to stand as a single phrase, a single condition in which excessive methylation of L-dopa is accompanied by neurodegeneration?