Nothing really, other then longer warm up time. It is very common on olds motors to do this for hot rod purposes. Be for warned that the aluminum blocker blocks you can buy tend to rattle a little. I blocked mine with a thin piece of sheet metal I placed in the turkey tray opening with some gasket sealer.
I lot of racers will fill it with molten aluminum, then they work it to be part of exhaust port, then heat risers are in the center 2 exhaust ports.
If I not certain that blocking off the heat riser is a permanent thing I shape an aluminum slug 3/8ths to 1/2 inch thick that is driven into the manifold side of the passage flush with the machined intake surface. Then use an intake manifold gasket set with the thin stainless exhaust crossover block off to isolate the aluminum driven into the intake from having hot exhaust gasses from playing directly on the plug. Note that intake gaskets with the built in restrictor stainless or not will burn through if not backed up.
If this is an iron intake it will be effing miserable to drive in cool to cold weather eventually these will warm up from engine heat but it will take 30-40 miles of driving for that to happen in cool weather maybe never in cold winter weather. Aluminum will warm up from engine heat in about 5 or 6 miles. With a carburetor getting an idle condition between the cold engine that is warm enough to be off the automatic choke but not yet heat soaked will drive you crazy trying to get a consistent idle speed when or if you drove enough to get the heat soaked condition. You’ll learn a lot about mixture quality‘s affect on drive ability as it pertains to street driving.
Race engine, block them off. Street engine, don't block them off because of drivability issues caused by reduced fuel vaporization and fuel puddling in the bottom of the intake manifold plenum. I know of many people that did block them off and then complain of drivability issues, then take it apart to remove the block offs. Opinions will vary.