Juvenile megaloblastic anaemia 1 (OMIM # 261100) is a rare autosomic disorder characterized by selective cobalamin mal-absorption and inconstant proteinuria produced by mutations in either CUBN or AMN genes. Amnionless, the gene product of AMN, is a transmembrane protein that binds tightly to the N-terminal end of cubilin, the gene product of CUBN. Cubilin binds to intrinsic factor-cobalamin co...

BACKGROUND Current tests for evaluation of vitamin B(12) absorption are problematic because they involve the use of radioactively labeled vitamin B(12). We describe a vitamin B(12) absorption test that circumvents this problem. METHODS We measured cobalamin or transcobalamin saturated with cobalamin (holo-TC) 24 h after three 9-microg doses of vitamin B(12) given orally at 6-h intervals. We s...

Cobalamin is an essential cofactor for enzyme systems, and adequate amounts are required for nucleic acid synthesis and hematopoiesis. The 2 most important reactions involving cobalamin are the conversion of methylmalonyl-coenzyme A to succinylcoenzyme A and the remethylation of homocysteine. Cobalamin deficiency leads to decreased activity of these enzyme systems, resulting in increased concen...

BACKGROUND Inherited malabsorption of cobalamin (Cbl) causes hematological and neurological abnormalities that can be fatal. Three genes have been implicated in Cbl malabsorption; yet, only about 10% of ~400-500 reported cases have been molecularly studied to date. Recessive mutations in CUBN or AMN cause Imerslund-Gräsbeck Syndrome (IGS), while recessive mutations in GIF cause Intrinsic Factor...

Three topics affecting cobalamin, folate, and homocysteine that have generated interest, activity, and advances in recent years are discussed. These are: (I). the application of an expanded variety of tools to the diagnosis of cobalamin deficiency, and how these affect and are affected by our current understanding of deficiency; (II). the nature of the interaction between homocysteine and vascu...