Cerebral folate deficiency in adults: A heterogeneous potentially treatable condition

Abstract Objective To describe the phenotype and the response to folinic acid supplementation of cerebral folate deficiency (CFD) in adults, a disorder diagnosed on low 5-methyltetrahydro-folate (5MTHF) in cerebrospinal fluid (CSF), which can correspond to a inherited disorder of folate metabolism (IDFM) or to a metabolic consequence of various neurological diseases. Methods We conducted a retrospective study on 224 adult patients with neurological symptoms who had a 5MTHF CSF dosage, collecting their neurologic and neuroimaging data. Results 69 patients had CFD (CSF 5MTHF level  p  = .01). In Magnetic Resonance Spectroscopy (MRS), Choline/Creatine (Cho/Cr) ratio was lower in sCFD patients ( n  = 7) compared to non-CFD patients ( n  = 73) ( p  = .005), with good sensitivity (71%) and excellent specificity (92%). Among twenty-one CFD patients treated with folinic acid, nine had a sustained improvement, all with sCFD but one (50% of sCFD patients improved). In two undiagnosed patients with extremely low 5MTHF CSF values, MRI WMA and low Cho/Cr ratios, folinic acid treatment leaded to a dramatic clinical and radiological improvement. Conclusion CSF 5MTHF dosage should be considered in patients with mitochondrial diseases, primary brain calcifications and unexplained complex neurological disorders especially if associated with WMA, since folinic acid supplementation in patients with sCFD is frequently efficient.