Dubbed the White Widow, Lewthwaite is wanted in connection with an atrocity in Kenya, her alleged role in bomb-making factories and terrorist activity in Yemen.
Born to a British soldier from England and a Northern Irish Catholic mother, Lewthwaite spent her early years in the family's home in Banbridge's Whyte Acres estate.
The claims caused Lewthwaite's frail grandmother to be taken to hospital in Northern Ireland, while those who knew her growing up in Aylesbury said they were "astonished and amazed".
Known as the White Widow, the 29-year-old mother-of-three is the daughter of English soldier Andy Lewthwaite, who met and married Irish Catholic Christine Allen while serving in Northern Ireland during the 1970s.
She enjoyed an unremarkable childhood in Banbridge, Co Down, before moving to Aylesbury at a young age. In 1995 her parents split.
After converting to Islam at 17, Lewthwaite changed her name to Sherafiyah and married Lindsay, who detonated the bomb at King's Cross Tube station, killing 26 people in July 2005.
At the time she claimed to have been horrified by the killings, but in 2009 disappeared with her three children and only resurfaced two years later after travelling to Kenya on a false passport.
Kenya's foreign minister, Amina Mohamed, has fuelled further speculation by claiming a British woman who has allegedly been involved in terrorism "many times before" was among the militants who laid siege to the Westgate mall, leaving at least six Britons dead.
As Lewthwaite's global notoriety peaked, the shockwaves reached Banbridge, where Lewthwaite's grandmother, Elizabeth Allen, was taken to hospital.
Family friends said the pressure of the situation has taken its toll on the pensioner's health and mental well-being.
She had been given a panic alarm to contact security services in case the terror suspect made contact.
Joan Baird, a veteran Ulster Unionist councillor in Banbridge who knows the family, said: "This is so distressing for everyone. Mrs Allen is 85 and she is in and out of hospital. It is just so distressing."
In Aylesbury there was disbelief that the "average, British, young, ordinary girl" who was a "follower not a leader" could have gone on to mastermind extremist acts.
Councillor Raj Khan, who knew Lewthwaite socially, said she was "pleasant and courteous" and had a "very great personality" but lacked confidence.
"She was not strong-headed. And that's why I find it absolutely amazing that she is supposed to be the head of an international criminal terrorist organisation," Mr Khan said.
Niknam Hussain, a former mayor of Aylesbury and current chairman of the independent advisory group at Thames Valley Police, also knew Lewthwaite.
He said: "I'm astonished and amazed. I can't believe it's true in any which way.
"Until they provide us with proof, I think it's innocent until proven guilty, to be honest."
Mr Hussain added: "To ascribe a level of sophistication that she could control a whole terrorist empire, I'm sorry, I don't think that Tom Clancy could write anything like that."
Mr Hussain also knew Lewthwaite's husband, and described him as seeming "perfectly normal".
Those who were acquainted with Lewthwaite as a youngster insisted she was not linked in any way to the Jamia Ghausia Mosque or to the mainstream Muslim community in Aylesbury despite her desire to "learn Islam quite deeply".
She met Lindsay, a Jamaican-born Muslim convert who never made a secret of his extremist views, on an Islamic chatroom.
Brought up by his mother in Huddersfield, West Yorkshire, where he alarmed his teachers by attempting to radicalise impressionable younger pupils, he went on to kill 26 people travelling between King's Cross and Russell Square on the Piccadilly line.
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