There are limited data on the use of folic acid as a treatment for children with autistic disorder (AD). Most experimentation thus far has focused on the effects of folic acid supplementation in small samples of males with fragile X syndrome (FRAX), and many of these participants did not meet criteria for AD but were said to exhibit autistic-like features. Initial case reports suggested folic acid might be an effective treatment for FRAX, some of which noted a reduced expression of the fragile site Xq27 in blood cultures. Subsequent work found that high doses of folic acid supplementation reduced the percentage of FRAX positive cells and increased plasma-folate concentrations among 9 males with FRAX. Autistic-like behaviors were said to improve for the 5 youngest participants (age range 3 years, 5 months to 9 years, 10 months); however, one adult, aged 49, developed an increase in motor activity and aggressiveness during treatment. His behavior returned to pretreatment levels following discontinuation of folic acid. In similar work, researchers employed a crossover design using 4 boys (ages 6 to 14) with comorbid autism and FRAX to assess efficacy of folic acid supplementation. Favorable behavioral changes were noted for 3 boys; however, for 2 of them, carryover effects of folic acid into the placebo period may have clouded the magnitude of potential differences in folic acid versus placebo effects. No changes throughout the trial were evidenced for the fourth child, who was also the oldest and the only one to have commenced puberty.