Objective: To determine the prevalence of C677T MTHFR gene mutation among children suffering from homocystinuria and the severity of clinical manifestations. Methods: 7 families (7 cases, 9 siblings and 12 parents) and 20 healthy age and sex matched subjects were tested for C677T MTHFR gene mutation using Polymerase chain reaction- restriction fragment length polymorphism (PCR-RFLP). Results: The results of this study revealed that the TT genotype frequency was high (42.9%) among homocystinuric cases while 57.1% of cases had the wild type (CC). Conclusion: This study revealed that the TT genotype frequency was high among homocystinuric cases, indicating a high prevalence of C677T MTHFR gene mutation among Egyptian homocystinuric cases. However, the presence of C677T mutation alone does not necessarily imply poor prognosis as other homocystinuric patients without this mutation had higher plasma homocysteine and worse clinical presentation.