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The Swede reeled off four birdies and an eagle in a whirlwind eight holes from the 10th before dropping his third stroke of the day at the par-five 18th.
Karlsson was one shot ahead of South Korean teenager Noh Seung-yul (66) and two in front of European Tour money-list leader Martin Kaymer, who was five-under through 15 holes.
The 41-year-old Karlsson was making his first competitive appearance at the final European Tour event of the season and he made it a memorable debut, going within a stroke of matching Lee Westwood’s course record 64 set in 2009.
‘I didn’t know that much about the course except I know there were a lot of low scores last year,’ he told reporters.
‘I think it’s one of those courses when if you’re playing well it’s easy to get close because the surfaces sort of feed the ball into the pins. When I missed though, it was difficult to save myself.’
Karlsson had four birdies and two bogeys in an outward 34 on a hot and steamy day in Dubai before he really caught fire on the inward stretch.
He birdied the 10th and 12th and eagled the 14th when his 110-yard wedge shot took one bounce and went straight into the cup.
Karlsson rolled in birdie putts of 20 and 18 feet at the 16th and 17th but found trouble off the tee at the last and failed to save par from 15 feet.
The former Ryder Cup player, like fellow Swede Henrik Stenson, has struggled with his health in recent times.
Karlsson was sidelined last year for several months after suffering from blurred vision caused by fluid behind the retina in his left eye.
The 2008 European order of merit winner was also struck down by glandular fever this season.
‘I feel pretty comfortable with where I am. There’s no blindness at the moment or any other diseases so things are good,’ added Karlsson with a laugh.
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