Methylmalonic Acidemia and Megaloblastic Anemia due to Congenital Intrinsic Factor Deficiency

Causes of vitamin B12 deficiency in children include decreased intake, abnormal absorption, and inborn errors of B12 transport and metabolism. Rare causes of abnormal cobalamin absorption include Imerslund-Grasbeck syndrome (IGS) and intrinsic factor deficiency (IFD). IGS and IFD are caused by defects in the genes CUBN, AMN, and GIF. We describe a 2 year old male who presented with severe megaloblastic anemia and methylmalonic acidemia. He was found to have a GIF heterozygous mutation c.79+1G>A associated with congenital gastric intrinsic factor deficiency and a novel variant c.960C>A in trans position. Few cases with his particular mutation and megaloblastic anemia have been reported. His unique presentation was characterized by an initial suspicion of myelodysplastic syndrome and a substantial increase in methylmalonic acid levels, which raised concerns about an inborn error of metabolism.