We described two unrelated patients with type 1 congenital generalized lipodystrophy born in the same Brazilian region presenting with the Leu124Serfs*26, a novel frameshift mutation in AGPAT2. Their clinical manifestations were characterized by early and severe cardiovascular disease, which suggests a possible association between this mutation and a more aggressive phenotype. Here, AGPAT2 is linked to generalized lipodystrophy.