The popular second-row had been due to face the Springboks in Pretoria but instead flew home yesterday following the news.
Wales coach Mike Ruddock said: 'Unfortunately Brent has had to return home and at the moment all our thoughts are with him and his family.'
That means veteran forward Gareth Llewellyn has been promoted from the replacements bench to make his 90th international appearance.
He will line-up in the second row alongside Deiniol Jones who wins only his third cap while fellow ex-Warrior Gethin Jenkins is called up as the only other change to the side that beat Argentina 35-20 in Buenos Aires last weekend.
Ruddock added: 'Deiniol was always going to start as I have had plenty of opportunities to see Gareth but due to the unfortunate circumstances we have had to change things around.
'I'm sure Deiniol is raring to go. He's trained very hard and will be looking to make an impact in his first start.
'He's a very physical player who loves getting stuck in with the tackling and hitting rucks and we will need that against South Africa. But he also has good handling skills with passing and at the lineout so he deserves his chance.'
Michael Owen will undergo a late fitness test amid concerns for a back injury.
WALES: Gavin Henson (Ospreys); Hal Luscombe (Dragons), Sonny Parker (Ospreys), Tom Shanklin (Blues), Shane Williams (Ospreys); Nicky Robinson (Blues), Dwayne Peel (Scarlets); Gethin Jenkins (Blues), Mefin Davies (Unattached) Adam Jones (Ospreys), Deiniol Jones (Blues), Gareth Llewellyn (Unattached), Dafydd Jones (Scarlets), Colin Charvis (Newcastle Falcons, Captain), Michael Owen (Dragons).
REPLACEMENTS: Huw Bennett (Ospreys), Duncan Jones (Ospreys), Darren Morris (Leicester Tigers), Jonathan Thomas (Ospreys), Michael Phillips (Scarlets), Ceri Sweeney (Dragons), Rhys Williams (Blues)