BLY,
Most in flight leaks/imbalances will be caught when a 'Fuel Imblance' warning is presented or during routine checks. The outfit I worked for checked for balance and 'burn + onboard' fuel at least every hour.
Transport category aircraft will have a checklist for 'fuel imbalance' which will start out by asking you to add the fuel on board and the fuel used. If you get a sum very close to departure fuel you indeed have a fuel imbalance and would proceed with the checklist.
If there was a discrepancy the 'fuel imbalance' checklist will direct you to the 'fuel leak' checklist.
best regards,
Bruce Waddington