A major explosion caused by a gas leak has reduced two residential buildings in Manhattan to rubble, killing two women and injuring 22 people, with a number of others missing.

New York Mayor Bill de Blasio described the incident as “a tragedy of the worst kind”, saying a number of people were still unaccounted for as firefighters battled to extinguish the blaze in East Harlem.

Witnesses said the explosion, which sparked inevitable reminders for some New Yorkers of the 9/11 terror attacks in 2001 that brought down the Twin Towers, felt like an earthquake.

There were 15 apartments in the two buildings that collapsed, de Blasio and city officials told reporters on Wednesday near the scene of the disaster at 116th Street and Park Avenue.

So far the only indication as to the cause of the blast was a call from an adjoining apartment building at 9.13am local time alerting energy company Con Edison to the smell of gas.

The explosion came barely 15 minutes later, sparking a major fire and engulfing the area in a column of dense white smoke.

The New York Fire Department got an emergency call at 9.31am, and firefighters were on the scene two minutes later.

“There was a major explosion that destroyed two buildings. The explosion was based on a gas leak,” de Blasio said.

The site of the explosion in East #Harlem in New York City, before and after the building collapse: pic.twitter.com/DjkpUrjviq

— snebbert (@snebbert) March 12, 2014

It is the first deadly disaster of its kind to strike the city of eight million since the Democrat took office in January and will raise concerns about safety in less affluent neighbourhoods.

“There was no indication in time to save people. We know we have lost two people already,” the mayor said.

“There is a tremendous amount of anxiety, but suffice it to say that every effort is being expended to locate each and every one of these (missing) individuals,” he added.

De Blasio was careful to caution that some of those missing could simply be safe elsewhere and out of contact.

A police spokesman said 22 people were injured – two were in critical condition and five others in serious condition.

Witnesses compared the explosion to an earthquake and what they saw to a war zone, after the blast ripped through their bustling city routine.

Train services in and out of Grand Central Station in midtown Manhattan were suspended as a result of the incident next to its tracks.

Hundreds of police and more than 250 firefighters were on site with emergency trucks, as a dense column of smoke spewed into the sky over the Metro-North railway line.