Imerslund-Gräsbeck Syndrome: Rare Cause of Megaloblastic Anemia in Well-Nourished Child

Megaloblastic anemia, characterized by macrocytic anemia, is most commonly caused by nutritional vitamin B12 deficiency; however, inherited disorders of cobalamin absorption should be considered in children with adequate dietary intake. One such disorder is Imerslund-Gräsbeck syndrome (IGS), a rare autosomal recessive condition characterized by selective intestinal malabsorption of vitamin B12 due to mutations in the CUBN or AMN genes.

The authors report a 7-year-old boy, born of a third-degree consanguineous marriage, who presented with generalized rash, easy fatigability, and recurrent oral ulceration. Examination revealed pallor and hyperpigmented knuckles without organomegaly. Growth parameters were between the 10th and 25th centiles.

Investigations showed severe macrocytic anemia (hemoglobin 2.5 g/dL), leukopenia, thrombocytopenia, markedly reduced vitamin B12 levels, and elevated homocysteine and methylmalonic acid concentrations. The patient was well-nourished, with no history of dietary restriction or malabsorption syndromes other than IGS.

This case highlights the importance of considering genetic causes of cobalamin malabsorption in pediatric patients presenting with megaloblastic anemia despite adequate nutritional intake. Identification of CUBN or AMN mutations is essential for confirming the diagnosis and guiding management strategies in laboratory research contexts.

The study underscores that IGS should be included in the differential diagnosis for macrocytic anemia when nutritional deficiencies are excluded. Researchers investigating metabolic pathways related to vitamin B12 transport may find this case relevant for understanding genetic mechanisms underlying selective malabsorption disorders.