Learn Italian: Sarà un grande fallimento per colpa della sua irresponsabilità. - It will be a huge failure because of his irresponsibility.

The core phrase is per colpa di (because of / by fault of). However, in Italian, you usually need a definite article before a possessive adjective like sua. When the preposition di meets the article la (from la sua), they combine to form the articulated preposition della.

Could I say a causa della sua irresponsabilità instead?

Yes, grammatically both are correct. However, per colpa di specifically assigns blame (literally meaning 'for fault of'). Because irresponsibility is a negative trait that directly caused a failure, per colpa di is a much stronger and more natural choice here than the neutral a causa di.

The English translation says 'his irresponsibility', so why is the feminine sua used?

In Italian, possessive adjectives agree with the gender and number of the thing being possessed, not the person who owns it. Because irresponsabilità is a feminine noun, it requires the feminine sua, regardless of whether the irresponsible person is a man or a woman.

How can I tell that irresponsabilità is a feminine noun?