Abstract

A 46-year-old woman was admitted for suspected early-onset dementia. At the age of 20 years, she presented with seizures. She was subsequently diagnosed with major depressive disorder and schizophrenia. At age 43, she developed muscular hypotonia and gait disturbance. Three years later, on admission, laboratory studies showed marked hyperhomocysteinemia, hypomethioninemia, and decreased folate level. Brain magnetic resonance imaging revealed multiple cerebral infarction. She received supplements with folate and vitamin B6. After the treatment, serum homocysteine level was reduced but serum folate level was elevated above normal. A diagnosis of methylenetetrahydrofolate reductase (MTHFR) deficiency was considered, so we changed folate to betaine. Sequence analysis of the MTHFR gene demonstrated a missense c.677C>T (p.Ala222Val) mutation. Treatment with betaine resulted in reducing the folic acid level to normal and physical rehabilitation improved the muscular hypotonia. However, psychiatric symptoms such as cognitive impairment and depressive symptoms did not improve during the disease course. This case suggests that measurement of serum levels of homocysteine, methionine, and folate may be useful for identifying the cause of unexplained adult-onset epilepsy, progressive neurological distress, and early-onset multiple cerebral infarction

Keywords: Methylenetetrahydrofolate reductase deficiency; Hyperhomocysteinemia; Multiple cerebral infarction; Betaine; Early-onset dementia