ImerslundGräsbeck

Imerslund-Gräsbeck syndrome, also known as Imerslund–Gräsbeck syndrome (IGS), is a rare autosomal recessive disorder characterized by selective malabsorption of vitamin B12 (cobalamin) due to a defect in the ileal uptake of the B12–intrinsic factor complex. The condition leads to lifelong megaloblastic anemia if untreated.

Genetics and pathophysiology

IGS results from mutations in the CUBN or AMN genes, which encode components of the cubilin–amnionless receptor complex on enterocytes. This complex mediates receptor-mediated endocytosis of the B12–intrinsic factor complex in the terminal ileum. Mutations disrupt intestinal absorption of vitamin B12 and, because cubilin is also involved in proximal tubular reabsorption of low molecular weight proteins, patients may develop mild renal proteinuria.

Clinical features

Onset is typically in childhood with progressive fatigue, pallor, and growth retardation. Megaloblastic anemia impairs development if untreated. Neurologic symptoms are less common early but can occur if treatment is delayed. Proteinuria may be present due to proximal tubule involvement and can serve as a supportive clue.

Diagnosis

Laboratory findings include low serum vitamin B12 with elevated methylmalonic acid and homocysteine. Intrinsic factor antibodies are absent, distinguishing IG S from pernicious anemia. Urinalysis may reveal low molecular weight proteinuria. Genetic testing identifying mutations in CUBN or AMN confirms the diagnosis; historical Schilling testing may show lack of correction with intrinsic factor.

Treatment and prognosis

Lifelong vitamin B12 replacement, usually by intramuscular injections, leads to hematologic and symptomatic improvement. Some patients can be managed with high-dose oral B12. With treatment, prognosis is favorable, and growth and development can normalize.

Eponym and discovery

The syndrome is named after Norwegian pediatrician Per Kristian Imerslund and Finnish physician Gry Gräsbeck, who described it in the 1960s.