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Senior Member (jccglutenfree)
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Join Date: Aug 2006
Location: Wisconsin
Posts: 1,581
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Senior Member (jccglutenfree)
Join Date: Aug 2006
Location: Wisconsin
Posts: 1,581
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Vitamin B-12 Associated Neurological Diseases
http://emedicine.medscape.com/article/1152670-overview
Quote:
Inadequate vitamin B-12 absorption is the major pathomechanism and may result from several factors. - Intrinsic factor deficiency
- PA accounts for 75% of cases of vitamin B-12 deficiency. It is an autoimmune attack on gastric IF. Antibodies are present in 70% of patients. They may block the formation of the cobalamin-IF complex or block its binding with cublin. Other antibodies are directed at parietal cell hydrogen-potassium adenosine triphosphatase (ATPase).
- Juvenile PA results from inability to secrete IF. Secretion of hydrogen ions and the gastric mucosa are normal. Transmittance is autosomal recessive inheritance of abnormal GIF on chromosome arm 11q13.
- Destruction of gastric mucosa can occur from gastrectomy or Helicobacter pylori infection. A Turkish study found endoscopic evidence of H pylori infection in more than 50% of vitamin B-12–deficient patients. Antibiotics alone eradicated H pylori in 31 patients, with resolution of vitamin B-12 deficiency.
- Deficient vitamin B-12 intake: Intake may be inadequate because of strict vegetarianism (rare), breastfeeding of infants by vegan mothers, alcoholism, or following dietary fads.
- Disorders of terminal ileum: Tropical sprue, celiac disease, enteritis, exudative enteropathy, intestinal resection, Whipple disease, ileal tuberculosis, and cublin gene mutation on chromosome arm 10p12.1 in the region designated MGA 1, which affects binding of the cobalamin-IF complex to intestinal mucosa (Imerslünd-Grasbeck syndrome), are disorders that affect the terminal ileum.
- Competition for cobalamin: Competition for cobalamin may occur in blind loop syndrome or with fish tapeworm (Diphyllobothrium latum).
- Abnormalities related to protein digestion related to achlorhydria: Abnormalities include atrophic gastritis, pancreatic deficiency, proton pump inhibitor use, and Zollinger-Ellison syndrome, in which the acidic pH of the distal small intestine does not allow the cobalamin-IF complex to bind with cublin.
- Medications: Medications include colchicine, neomycin, and p -aminosalicylic acid.
- Transport protein abnormality: Abnormalities include transcobalamin II deficiency (autosomal recessive inheritance of an abnormal TCN2 gene on chromosome arm 22q11.2-qter resulting in failure to absorb and transport cobalamin) and deficiency of R-binder cobalamin enzyme.
- Disorders of intracellular cobalamin metabolism: These disorders result in methylmalonic aciduria and homocystinuria in infants.
- Isolated methylmalonic aciduria
- Cbl A is due to deficiency of mitochondrial cobalamin reductase resulting in deficiency of adenosylcobalamin.
- Cbl B is due to deficiency of adenosylcobalamin transferase resulting in deficiency of adenosylcobalamin.
- Methylmalonic aciduria and homocystinuria
- Cbl C is a combined deficiency of methylmalonyl CoA mutase and homocysteine:methyltetrahydrofolate methyltransferase. Patients have prominent neurologic features and megaloblastic anemia.
- Cbl D is a deficiency of cobalamin reductase. Patients have prominent neurologic features.
- Cbl F is a defect in lysosomal release of cobalamin.
- Isolated homocystinuria
- Cbl E is due to a defect in methionine synthase reductase located on chromosome arm 5p15.3-p15.2.
- Cbl G is due to a defect in methyltetrahydrofolate homocysteine methyltransferase located on chromosome arm 1q43.
- Increased vitamin B-12 requirement: Requirement is increased in hyperthyroidism and alpha thalassemia.
- Other causes
- In AIDS, vitamin B-12 deficiency is not infrequent. Although the exact etiology remains obscure, it is likely a multimodal process involving poor nutrition, chronic diarrhea, ileal dysfunction, and exudative enteropathy. Low vitamin B-12 levels may be more common in late than in early HIV disease.
- N 2 O exposure can occur iatrogenically (ie, anesthesia) or through abuse ("whippets").
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This is an exellent, readable, report on B12 deficiency:
Vitamin B12 Deficiency
http://www.aafp.org/afp/20030301/979.html
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