Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0024523 (malabsorption)
 7,319 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In a prospective study of thirty five consecutive patients with decreased plasma cobalamine (P-Cbl), twenty-two (63%) were diagnosed as having pernicious anaemia (PA) (no age or sex differences) on basis of the B12-absorption test and/or megaloblastic changes in the bone marrow. In this group ten patients were anaemic (six of whom were characterized as macrocytic), sixteen of nineteen examined had megaloblastic changes in the bone marrow, and all of thirteen examined had achlorhydria with positive correlation to Parietal Cell Antibodies (PCA). Two patients with PA had normal Cbl-absorption and two had malabsorption at the time of diagnosis. Twenty-one patients (95%) had PCA and thirteen (59%) were Intrinsic Factor Antibody (IFAb) positive. Three patients IFAb-seroconverted within a year. Among the remaining thirteen patients (37%), one had PCA but not IFAb and three were IFAb-positive all of whom had normal Cbl-absorption. Of the three patients with IFAb one had also PCA, one IFAb-seroconverted within three months, and one had microcytic anaemia with iron depleted bone marrow due to coecal cancer. Among twenty two healthy adult controls four (18%) had PCA while none had IFAb. This investigation shows that at the debut half of PA patients (55%) do not have anaemia, some have normal Cbl-absorption and some have malabsorption. 95% have PCA and 59% have IFAb. So, IFAb-negative PA is often seen (41%) and seroconversion can take place. Diagnosis is even more reliable, when achlorhydria is present in PCA-positive persons. Healthy PCA-positive persons are probably predisposed to develop PA. Patients with cbl-deficiency, IFAb and/or PCA must be considered as having latent PA even if they have normal haemoglobin and normal Cbl-absorption. These patients should be followed and, in case of anaemia or signs of neuropathia, treated.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:[Pernicious anemia. A study of initial forms of the disease and diagnostic significance of determination of the intrinsic factor antibody and parietal cell antibody]. 846 Apr 41

Inherited disorders of vitamin B12 include those which involve the inability of the vitamin to be absorbed from the gut and transported to the appropriate tissues, and those in which the vitamin is not utilised by target cells. The former include intrinsic factor abnormalities, selective malabsorption of vitamin B12 with proteinuria, and deficiencies of transcobalamin I and transcobalamin II. The latter include a defect in the release of free vitamin B12 from lysosomes (cblF), and defects in the formation of both vitamin B12 cofactors (cblC, cblD) or of adenosyl-B12 (cblA, cblB) or methyl-B12 alone (cblE, CblE variant). This article reviews the major clinical manifestations of these diseases, and provides an approach to the diagnosis of transcobalamin II deficiency and the cbl mutations using cultured cells.
 ...
PMID:Inherited disorders of vitamin B12 metabolism. 333 1

Deficient activity of an enzyme can result from a defect in the conversion of the vitamin to a co-enzyme as well from an abnormal apo-enzyme or disturbed binding of coenzyme to enzyme. Conversion of dietary vitamin to intracellular active co-enzyme can be complex and require many physiological and biochemical processes including stomach release of bound vitamin, intestinal uptake, carriers/transport, blood transport, cellular uptake, intracellular release and intracellular compartmentalisation. Disorders of malabsorption (food cobalamin malabsorption, intrinsic factor deficiency and abnormal enterocyte cobalamin processing) and transport proteins (transcobalamin II deficiency, R-binder deficiency) mostly lead to disturbed function of the two cobalamin requiring enzymes, methylmalonyl CoA mutase and methionine synthase. Defects of early steps of intracellular cobalamin (cblF, cbl C/D) result in marked deficiencies of both cobalamin co-enzymes and homocystinuria combined with methylmalonic aciduria. Defective synthesis of adenosyl cobalamin in the cbl A/B defects leads to methylmalonyl CoA mutase. Isolated methionine synthase deficiency is also classified as a cobalamin disorder due to its associated deficient formation of methylcobalamin. Folate disorders include methylene-tetrahydrofolate reductase deficiency and glutamate formimino-transferase deficiency. In addition a hereditary disorder of intestinal folate transport has been described. Less well established are disorders of dihydrofolate reductase, methenyl-tetrahydrofolate cyclohydrolase, and defects of cellular folate uptake.
 ...
PMID:Genetic defects of folate and cobalamin metabolism. 958 28