A statement issued by the J9 Foundation announced Springbok icon Joost van der Westhuizen was taken to hospital on Saturday.
South Africa Rugby President Mark Alexander said: "Joost will be remembered as one of the greatest Springboks - not only of his generation, but of all time". He will be sorely missed'.
Joost's legacy will forever be emblazoned as the best ever player to don the Springbok, and the Blue Bulls for that matter, jersey. On behalf of the Government and the people of South Africa, our heartfelt condolences to Mr van der Westhuizen's family. But that hasn't stopped him from taking part in ALS research and drives.
In 2015, a fragile van der Westhuizen joined fellow 1995 World Cup champions at Ellis Park Stadium for an event to commemorate 20 years of the team's historic victory. He wasn't as vocal as the likes of George Gregan or Matt Dawson when I was playing against him. He was lethal around the fringes.
"Throughout the period that Joost had his motor neurone and he was doing a wonderful job with his J9 foundation. that again was typical of the man that he didn't put himself first".
It is an incredibly sad day and he will leave a big gap in our hearts. Let us not forget his spirit and his life.
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"We are surrounded by family and much love".
His off-field battles began in 2011, when he was diagnosed with motor neurone disease, and he was given between two and five years to live.
"Rugby world lost another great person and player", former Wallabies back David Campese tweeted.
I'm absolutely gutted! One of my heroes growing up!
"He was a fantastic rugby player and for me was the best nine I played against".
"Great memories with our dear friend and team mate, laughing eyes even in the face of adversity!"