Inherited megaloblastic anemia caused by a
constitutional malabsorption of vitamin B12.
Defect of Enterocyte Intrinsic Factor Receptor;
Enterocyte Cobalamin Malabsorption; Imerslund-Grasbeck Syndrome;
Imerslund-Najman-Grasbeck Syndrome; Juvenile Pernicious Anemia due to
Selective Intestinal Malabsorption of Vitamin B12 with Proteinuria.
Internationally, the incidence of megaloblastic anemia
in childhood is not established; however, 29 cases have been reported in the
Middle East between 1960 and 1998.
Autosomal recessive with multiple nonallelic
forms. Gene map locus is 10p12.1.
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 not
influenced by the administration of intrinsic factor. Renal function studies
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.
Megaloblastic anemia that responds to parenteral
cobalamin administration. Proteinuria. This condition has been associated
with dolichocephaly, confusion, dementia, generalized paresthesias, and sensory
Mandatory to obtain a complete blood
cell (CBC) count, vitamin
B12 plasma level, and urinary protein level.
Consider postponing elective surgery in
face of untreated anemia. In case of surgical emergency, complete
type and crossmatch for blood must be obtained.
Theoretically, nitrous oxide should
be avoided because it reduces the activity of the vitamin B12-dependent
enzymes methionine synthetase and thymidylate synthetase.
Other causes of megaloblastic
anemia by deficiency of either vitamin B12 or folinic acid:
Vitamin B12 Deficiency: Impaired absorption
(insufficient release of vitamin B12 from protein, intrinsic factor
deficiency, chronic pancreatic or intestinal disorders, parasitoses) or
inadequate utilization (defective enzymes, lack of transcobalamin II,
chronic exposure to nitrous oxide).
Folic Acid Deficiency: Prematurity, insufficient dietary
intake, alcoholism, intestinal derivation, tropical sprue, treatment with
sulfasalazine or folic acid antagonists such as methotrexate, hemodialysis.
Ben-Ami M: Imerslund syndrome with dolichocephaly. Pediatr Hematol Oncol
Gueant JL, Chery C, Namour F, et al: Decreased affinity of urinary intrinsic
factor-cobalamin receptor in a case of Grasbeck-Imerslund syndrome.