Methylenetetrahydrofolate reductase (MTHFR) deficiency is a rare autosomal 
recessive disorder. It is known that MTHFR deficiency may result in 
hyperhomocysteinemia, but MTHFR deficiency-induced schizophrenia has been rarely 
reported. Here we present the clinical course, biochemical and genetic 
characteristics of schizophrenia resulted from MTHFR deficiency in a school-age 
boy. He was 13 years old. He was admitted with a two-year history of fear, 
auditory hallucination, learning difficulty, sleeping problems, irascibility, 
drowsing and giggling. At admission, he had significantly elevated plasma and 
urine levels of total homocysteine, significantly decreased levels of folate in 
serum and cerebrospinal fluid, and a normal blood concentration of methionine. 
Further DNA sequencing analysis showed 665C>T homozygous mutations in the MTHFR 
gene. The patient was diagnosed with MTHFR deficiency-associated schizophrenia 
and treatment with calcium folinate, vitamin B12, vitamin B6, and betaine was 
initiated. After the treatment for 1 week, his plasma and urine levels of 
homocysteine were decreased to a normal range and the clinical symptoms were 
significantly improved. After 3 months of treatment, the patient returned to 
school. He is now living with normal school life. In summary, children with 
late-onset MTHFR deficiency and secondary cerebral folate deficiency may lead to 
schizophrenia. This rare condition can be early diagnosed through analyses of 
blood and urine total homocysteine, amino acids in blood and folate in blood and 
cerebral fluid and successfully treated with folinic acid, vitamin B6, vitamin 
B12 and betaine.