It's find as being a Campaign Guide, have it give a list of what is allowed and what isn't and then have it offer Tkreen, Muls, and so on. Most of the basic rules remain in place, such as advantage.
So what is or isn't allowed? Lets keep it JUST PHB options (no Volo, SCAG, etc).
Races:
Human (as is)
Elf - Well considering Athasian elves aren't like normal elves, would you make a whole new subrace or limit it to just one subrace (no high or drow)? -2 options.
Dwarf - See Elf. (-1 option)
Halfling - See Elf (-1 option)
Dragonborn - 4e made them Dray. Lets assume we keep that, else -1 option.
Gnome - Don't exist. -2 options.
Half-elf - Fine? Maybe?
Half-orc - Don't exist. -2 options.
Tieflings - Well, they were in 4e DS again. Else, -1 option.
Half-giant - Either refluffed goliaths or thier own race +1 option.
Muls - New race +1 option.
Thri-kreen - New race +1 option.
Losses between -7 and -9, depending on your option of 4e's version. Gains +3.
Classes (note, I count one option lost per subclass, plus an additional if the base class is also not usable as that would stop future subs that might work for the setting to work).
Barbarian - I've heard some DS fans say that unarmored defense breaks the setting's equipment system and shouldn't be allowed. Assuming we do, there is no bears, wolves, or eagles so Totem seems out of the question, though berserker seems to work fine. -1 option (-3 if no class at all).
Bard - Again, 4e allowed spellcasting bards (3.5 Dragon did too) but purists argue they shouldn't and should best be Rogue-assassins. Assuming we allow them, there doesn't seem to be an issue. If not, -3 options.
Cleric - Elemental Priests were present in 2e and 3.5, but not 4e. If allowed, the only domains that make sense are tempest and nature. -5 options, unless you go 4e and -8 options.
Druid - Well, Circle of the land might get a nerf, but its still viable. Not sure about Moon. Play it safe- all options.
Fighter - No eldritch knight. Others fine. -1 options.
Monk - 3e and 4e had them, but see barbarian for UAD and add superior martial arts dice. All the subs seem fine if your allowing them at all. All options OR -4 options.
Paladin - 3e found room for them, nobody else has and they seem to be the posterboy for exclusion. -4 options.
Ranger - Fine? All options.
Rogue - No arcane trickster - 1 options.
Sorcerer - 3e and 4e found them homes, but all arcane classes depend on how you plan on doing defiling. At the very least, dragonblooded isn't an option with the setting changes to dragon. Wild magic possibly? -1 to -3 options.
Warlock - 4e made them templars. Either way, no fiend, GOO and archfey possible? -1 to -4 options.
Wizard - See sorcerer. If preserving/defiling works with the school system, then no changes. Else, -8 options.
Psionics - Mearls last HFH seemed to lean on muliple subs, for wizard, fighter, bard, rogue and monk as well as its own class. Lets assume they do that. +8 options.
Losses Between -14 (most lenient) to -32 (most restrictive) options removed. +8 options minimum. Thats a lot of subclasses that need replacing. At worst, we also lose up to 7 of the 13 classes at most restrictive.
Which goes back to my point; if your cutting that much, you better do more than three new races and psionics. You've cut up to half the PHB! You could, of course, replace cut options with new appropriate options (new races, subraces, subclasses, and even classes) and do the same with equipment (an utterly useless chapter in the PHB for DS) backgrounds (again, some might work, others aren't) and spells (Melf who?). Also, most of the Appendixes are useless, cut them too.
Huh, that's a lot of new material you need to replace; probably a majority of the book. And that doesn't get into rules like weapon breakage or defiling and preserving or desert survival. It starts to look like... wait, we might need, an alternate Player's Handbook to put all these things in one place?
Oh, and lets not bother looking at the Monster Manual. That's going to be fun to go through and decide what does and doesn't exist...