You can fly with one just fine. There are multiple restrictions added, depending on type. Some are only allowed to ferry to a repair station on a non
revenue flight, but if you remove one, you get an increase in fuel consumption. The 747-400 is about 2.5%.
Surprisingly, looking at the minimal equipment list, you can fly with one missing but not with both missing.
And yes, it increases fuel burn amongst other issues like decreased lift etc.