5-methyltetrahydrofolate and Atrophy

We examined whether using a medical food therapy for hyperhomocysteinemia (HHcy) in patients with Alzheimer's disease (AD) or cognitive impairment due to cerebrovascular disease (CVD) with Cerefolin®/CerefolinNAC® (CFLN: L-methylfolate, methylcobalamin, and N-acetyl-cysteine) slowed regional brain atrophy. Thirty HHcy patients with AD and related disorders (ADRD) received CFLN (HHcy+CFLN: duration [μ ±  σ] = 18.6±16.1 months); a sub-sample of this group did not receive CFLN for varying periods of time (HHcy+NoCFLN: duration [μ ±  σ] = 12.6±5.6 months). Thirty-seven NoHHcy patients with ADRD did not receive CFLN (NoHHcy+NoCFLN: duration [μ ±  σ] = 13.3±17.7 months). No participant took supplemental B vitamins. Regional brain volumes were measured at baseline and end of study, and covariate-adjusted rates of hippocampal, cortical, and forebrain parenchymal (includes white matter) atrophy were predicted. The HHcy+CFLN group's hippocampal and cortical atrophy adjusted rates were 4.25 and 11.2 times slower than those of the NoHHcy+NoCFLN group (p < 0.024). The HHcy+CFLN group's forebrain parenchyma atrophy rate was significantly slower only for CVD; the rate of slowing was proportional to the degree of homocysteine lowering (p < 0.0001). CFLN was associated with significantly slowed hippocampal and cortical atrophy rates in ADRD patients with HHcy, and forebrain parenchymal atrophy rates in CVD patients with HHcy. The present results should be further validated.

Topics: Acetylcysteine; Aged; Aged, 80 and over; Alzheimer Disease; Atrophy; Cerebral Cortex; Cerebrovascular Disorders; Dietary Supplements; Female; Humans; Hyperhomocysteinemia; Male; Middle Aged; Tetrahydrofolates; Vitamin B 12; Vitamin B Complex; White Matter

Folinic acid-responsive seizures (FARS) are a rare treatable cause of neonatal epilepsy. They have characteristic peaks on CSF monoamine metabolite analysis, and have mutations in the ALDH7A1 gene, characteristically found in pyridoxine-dependent epilepsy. There are case reports of patients presenting with seizures at a later age, and with folate deficiency due to different mechanisms with variable response to folinic acid supplementation. Here, we report 2 siblings who presented with global developmental delay and intractable seizures who responded clinically to folinic acid therapy. Their work-up included metabolic and genetic testing. The DNA sequencing was carried out for the ALDH7A1 gene, and the folate receptor 1 (FOLR1) gene. They had very low 5-methyltetrahydrofolate (5-MTHF) in CSF with no systemic folate deficiency and no characteristic peaks on neurotransmitter metabolite chromatogram. A novel mutation in the FOLR1 gene was found. The mutation in this gene is shown to affect CSF folate transport leading to cerebral folate deficiency. The response to treatment with folinic acid was dramatic with improvement in social interaction, mobility, and complete seizure control. We should consider the possibility of this treatable condition in appropriate clinical circumstances early, as diagnosis with favorable outcome depends on the specialized tests.

Topics: Atrophy; Brain; Brain Diseases, Metabolic, Inborn; Child Development Disorders, Pervasive; Child, Preschool; Consanguinity; Developmental Disabilities; Early Diagnosis; Electroencephalography; Epilepsies, Myoclonic; Female; Folate Receptor 1; Folic Acid Deficiency; Humans; Leucovorin; Magnetic Resonance Imaging; Male; Mutation, Missense; Point Mutation; Pyridoxine; Siblings; Tetrahydrofolates

Topics: Antiparkinson Agents; Atrophy; Basal Ganglia; Brain Diseases, Metabolic; Carbidopa; Cerebellum; Demyelinating Diseases; Dystonia; Female; Folic Acid Deficiency; Humans; Leucovorin; Levodopa; Male; Syndrome; Tetrahydrofolates; Treatment Outcome; Vitamin B Complex

Topics: Asian People; Atrophy; Basal Ganglia; Cerebellum; Humans; Male; Myelin Sheath; Tetrahydrofolates