Hohenheim is the philosopher's stone which was formed when the first homunculus tricked him and ate an entire country. He gave half the souls to Hohenheim as thanks but took Hohenheim's appearance when he made his own body.
Hohenheim did not have some lady partner. Envy is not his kid. Homunculus are not made from failed human transmutation but when the Hohenheim clone decides he wants to make one because he is fucking powerful and can cancel out the alchemy of Amestris at will.
Wrath isn't their master's son. Wrath is the Fuhrer. Pride is the fuhrer's son
. Lust is not some messed up incarnation of Scar's brother's girlfriend. Sloth isn't Ed and Al's mom. It's some random huge guy that's been digging a giant transmutation circle underneath Amestris. The entire foundation of the country was so the Hohenheim clone could use the souls of the people in order to become even more powerful.
Scar killed Winry's parents not Mustang. Hughes is still dead. Mustang's been discovered by the Fuhrer to be trying to stop him and it turns out the ENTIRE UPPER GOVERNMENT is corrupt and trying to gain immortality. They separate all of Mustang's subordinates to keep him weak.
There's a guy from FMA China that wants to gain immortality. He took in the power of Greed who had previously died and became a homonculus but is waiting to regain his body.
That should be the most basic overview of what's happened that's different from the anime.