The flames broke out around 9:30 a.m. in a fifth-floor apartment on East 153rd Street in the Melrose Houses.
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Authorities say the child, identified as Billay Jagana, suffered smoke inhalation and was pronounced dead at Lincoln Hospital.
Related: Man accused of torching his old apartment during standoff
The other victim, a 38-year-old woman believed to be Jagana's mother, is in critical condition also at Lincoln Hospital.
Officials have not released details on their relationship, but a man at the scene told Eyewitness News that the child was his nephew.
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"Nothing yet, I don't have no clue right now," Saikou Jagana said. "I was on the job site. One of my relatives called me. They say my brother's apartment had a fire. That's why I'm here."
Two firefighters suffered minor injuries battling the blaze, which took about 45 minutes to contain.
"I am deeply sorry, especially a little kid at this age, he is an angel," said Muhammadou Sillah, the victim's in-law. "I asked God to bless him."
Related: 2 firefighters injured after fire rips through NYC bike shop
There is no word yet on the cause of the fire, and the investigation is active and ongoing.
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