A 4‐year‐old girl presented with failure to thrive, frequent vomiting and regression of developmental skills. She appeared pale and had tachycardia (139 beats/min), glossitis and angular cheilosis. Laboratory testing showed pancytopenia with macrocytic anaemia, a haemoglobin level of 43 g/l (normal range for age 112–140 g/l) and mean corpuscular volume of 86.6 fl (75–85 fl); there was proteinuria, 750 mg/l (0–120 mg/l), and low levels of vitamin B12, <111 pmol/l. A blood film showed anisopoikilocytosis, hypersegmented neutrophils, megaloblasts and Cabot rings, indicative of megaloblastic anaemia (images). Blood transfusion and intramuscular cyanocobalamin were given. In the absence of common causes of vitamin B12 deficiency and in the light of the proteinuria, Imerslund–Gräsbeck syndrome was suspected; genetic testing revealed a pathogenic homozygous mutation in the amnionless gene (AMN; c.208‐2A>G).
Imerslund–Gräsbeck syndrome is a rare autosomal recessive disease causing vitamin B12 deficiency that may be associated with proteinuria. Mutations in either of two genes (CUBN or AMN) encoding the proteins cubilin and amnionless, which are expressed in ileal cells, result in selective vitamin B12 malabsorption. With monthly intramuscular cyanocobalamin supplementation, psychomotor development rapidly improved and haematological values fully normalised.
