Late on Tuesday, riot police had been sent in to quell the unrest. A cook of the shelter also died, while dozens more remain under treatment at a hospital in Guatemala City. The shelter is severely overcrowded, housing hundreds more than its 400 person capacity.
On Wednesday, anxious family members had gathered outside the home, while others rushed to hospitals to see if their relatives were there.
President Jimmy Morales declared three days of national mourning and pledged the Government's support for a transparent investigation.
"She said the girls told her that they had been raped and in protest they escaped, and that later, to protest, to get attention, they set fire to the mattresses", he said. It is not yet clear what caused the fire.
"We are going to ask for the immediate closure of the center, and attribute administrative and criminal responsibility against those in charge of the center for not fulfilling their duty", she said.
Plagued by Latin America's highest rates of child malnutrition and street gangs that often prey on minors, Guatemala has always been a traumatic place to grow up.
The BBC reported that the shelter takes in children who have been abandoned, suffered abuse or have been the victims of human trafficking. The Central American nation's public institutions are underfunded, racked by corruption and widespread overcrowding.
The wounded arrived in the hospital in the morning, some half naked, with bright pink burns and large pieces of skin that were dislodged from the body.
Guatemala's Justice Ministry said it would investigate a fire at a state-run juvenile home near Guatemala City that left at least 21 dead on Wednesday, local media reported.
" 'We had 15-19 new arrivals a day, every carer had 34 children to look after, and we were on one day on, one day off shifts of 24 hours because there were not enough staff, ' the employee said, adding she faced death threats and verbal abuse from her wards."
Rosa Aguirre, a 22-year-old street vendor who rushed from the capital to see if her two sisters, aged 13 and 15, and her 17-year-old brother were among the casualties, said authorities had given no information to relatives.