Here, we report a heterozygous variant in the gene encoding acetyl-coenzyme A acyltransferase 2 (ACAA2), a mitochondrial fatty acid β-oxidation (mFAO) enzyme, in 4 families with FPL, lipomatosis, and variable occurrence of infantile steatohepatitis and hypoglycemia (IHH). Here, ACAA2 is linked to lipomatosis.