We found that the occurrence of at least one PlA2 allele or two alleles (homozygote) for the C677T polymorphism of MTHFR presented a significantly increased risk of having Catterall III or IV LCPD (p = 0.05); thus, their screening in at-risk children might be useful in the future as prognosis markers. Here, MTHFR is linked to Legg-Calve-Perthes disease.