Imerslund-Grasbeck syndrome
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor-in-Chief Aditya Govindavarjhulla, M.B.B.S. [2]; Assistant Editor-in-Chief: Robert Shafton
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Overview
Imerslund-Grasbeck syndrome or Imerslund-Najman-Grasbeck syndrome or Imerslund-Grasbeck disease (IGS or INGS) is an autosomal recessive, familial form of vitamin B12 deficiency caused by malfunction of the receptor located in the terminal ileum.
Signs and symptoms
Defined as those seen in any macrocytic, megaloblastic anemia:
- Anemia: causing fatigue, conjuctival palor, pale complexion, and in some cases, a mild icterus (yellowing of the eye).
- Glossitis("shiny tongue"): shiny, glossy tongue.
- Cheilosis(stomatitis): Inflammation of the edges of the lips and the oral mucosa.
- Tabes dorsalis ("subacute combined degeneration of the spinal cord"): This involves the posterior section of the spinal cord and therefore involves proprioception (sense of position), touch, sense of vibration and in severe cases the lateral corticospinal tract, causing spastic paralysis of the limbs.
- Peripheral neuropathy: tingling sensation in the arms and legs.
- Pancytopenia: decreased number of blood cells, due to decreased bone marrow production.
- Methylmalonyl CoA-emia: defined as blood having and unusually high concentration of methylmalonyl CoA.
- Peripheral findings such as hypersegmented neutrophils and large RBCs on high field view of the blood smears.
- Laboratory findings indicating increased MCV (Mean Corpuscular Volume), decreased Hgb/Hct (indicating anemia), and decreased value of vitamin B12 in the blood.
- Proteinuria: protein found in the urine detected by analysis or by dipstick.
- Reversal of all symptoms except neurological symptoms, by IV injection of vitamin B12.
- Schilling test indicating no radioactive vitamin B12 in the urine. (This test has dropped out of favor and should not be tried in patients with any form of renal failure).
Genetics
The disease is autosomal recessive, and can therefore skip generations. Mutations in either amnionless (AMN) or cubilin can be the culprit. The suspected chromosome is 14.[1] Due to its autosomal recessive pattern of inheritance, affected individuals (persons possessing a homozygous recessive genotype) need to undergo genetic counselling to identify risk of family members who might be heterozygous genetic carriers.
Treatment
Since the essential pathology is due to the inability to absorb vitamin B12 from the bowels, the solution is therefore injection of IV vitamin B12. Timing is essential, as some of the side effects of vitamin B12 deficiency are reversible (such as RBC indices, peripheral RBC smear findings such as hypersegmented neutrophils, or even high levels of methylmalonyl CoA), but some side effects are irreversible as they are of a neurological source (such as tabes dorsalis, and peripheral neuropathy). High suspicion should be exercised when a neonate, or a pediatric patient presents with anemia, proteinuria, sufficient vitamin B12 dietary intake, and no signs of pernicious anemia.
References
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