Fatigue, which is a feeling of extreme tiredness, weakness, or exhaustion is the first symptom of almost every medical problem, including MTHFR. It can be linked to almost every body system, and it is the most general symptom we have. It is also linked to a number of common gene SNPs, including MTHFR, , fast MAOA, fast COMT, and many more. It is also tied to lifestyle factors like poor diet, lack of nutrients, poor or not enough sleep, and stress. So actually, in light of all of that, it is a bit surprising that any of us don't feel fatigued.