Imerslund-Gräsbeck Syndrome

At a glance

Imerslund Syndrome is an inherited megaloblastic anemia caused by a constitutional malabsorption of vitamin B12 (cobalamin) and caused by the malfunction of the “Cubam” receptor in the terminal ileum. Clinically, this medical condition is characterized with a macrocytic, megaloblastic anemia, proteinuria (50% of patients), glossitis, cheilosis, and peripheral neuropathy. The presence of failure to thrive, recurrent gastrointestinal or respiratory infections, pallor, and fatigue must alert to the megaloblastic anemia. It is not present at birth. Patient age at diagnosis varies from late infancy period to about 14 years old.

Synonyms

Defect of Enterocyte Intrinsic Factor Receptor; Enterocyte Cobalamin Malabsorption; Imerslund Syndrome; Imerslund-Najman-Grasbeck Syndrome; Juvenile Pernicious Anemia due to Selective Intestinal Malabsorption of Vitamin B12 with Proteinuria.

Incidence

Internationally, the incidence of megaloblastic anemia in childhood is not established. About 300 cases have been published thus far worldwide, with new cases predominantly appearing in eastern Mediterranean countries. Twenty-nine cases have been reported in the Middle East between 1960 and 1998. The syndrome was first described in Finland and Norway. The prevalence is approximately 1 in 200,000.

Genetic inheritance

Autosomal recessive with multiple nonallelic forms. Gene map locus is 10p12.1.

Pathophysiology

Megaloblastic anemia secondary to B12 malabsorption with proteinuria. The disease is caused by a selective defect between the attachment of B12 to the ileal cell surface and binding to transcobalamin II or absence of functional receptor (cubilin). It is caused by the malfunction of the “Cubam” receptor in the terminal ileum. This receptor is composed of two proteins, amnionless (AMN), and cubilin. It is not influenced by the administration of intrinsic factor. Renal function studies are normal.

Diagnosis

Bone marrow exam shows megaloblastic anemia. The Schilling test, which assesses cobalamin absorption both with and without exogenous intrinsic factor, is abnormal. Urinalysis reveals proteinuria despite otherwise normal renal function studies.

Clinical aspects

Megaloblastic anemia that responds to parenteral cobalamin (vitamin B12) administration. The presence of proteinuria is often seen. This condition has been associated with dolichocephaly, confusion, dementia, generalized paresthesias, and sensory deficits.

Precautions before anesthesia

Mandatory to obtain a complete blood cell (CBC) count, vitamin B12 plasma level, and urinary protein level.

Anesthetic considerations

Consider postponing elective surgery in face of untreated anemia. In case of surgical emergency, complete type and crossmatch for blood must be obtained.

Pharmacological implications

Theoretically, nitrous oxide should be avoided because it reduces the activity of the vitamin B12-dependent enzymes methionine synthetase and thymidylate synthetase.

Other conditions to be considered

Other causes of megalob­lastic anemia ...