TCII deficiency rarely if ever presents with neurologic manifestations. However, neurologic disorders can be produced subsequently by improper treatment. [ncbi.nlm.nih.gov]

• Recurrent Infection

  Other features include methylmalonic aciduria, recurrent infections, and vomiting and diarrhea. [diseaseinfosearch.org]

  Several medications may depress immunoglobulin and antibody levels, and this may result in recurrent infections. [primaryimmune.org]

• Ulcer

  A female infant presented at seven weeks of age with failure to thrive, progressively severe pancytopenia, hypogammaglobulinemia and, mucosal ulceration. [ncbi.nlm.nih.gov]

  Patients present with one or more of the following signs: weight loss, failure to thrive, diarrhea, vomiting, lethargy, irritability, pallor, ulcers of oral mucous membranes and impaired development. [orpha.net]

  The first signs of transcobalamin deficiency are typically a failure to gain weight and grow at the expected rate (failure to thrive), vomiting, diarrhea, and open sores (ulcers) on the mucous membranes such as the lining inside the mouth. [ghr.nlm.nih.gov]

  […] absorption), Zollinger-Ellison syndrome (gastrinoma causing peptic ulcer and diarrhea), or Crohn's disease. [aafp.org]

  Other Causes Individuals with chronic gastrointestinal conditions such as indigestion or peptic ulcers which recur frequently may have other underlying causes such as a gastrinoma leading to Zollinger-Ellison syndrome, Crohn’s disease, or rare deficiencies [news-medical.net]

• Irritability

  Patients present with one or more of the following signs: weight loss, failure to thrive, diarrhea, vomiting, lethargy, irritability, pallor, ulcers of oral mucous membranes and impaired development. [orpha.net]

  A vitamin B12 deficiency in children often presents itself with non-specific symptoms such as developmental delays, a diverging growth curve, anorexia, irritability, neurological problems and weakness. [stichtingb12tekort.nl]

  […] anemia Pancytopenia (leukopenia, thrombocytopenia) Neurologic Paresthesias Peripheral neuropathy Combined systems disease (demyelination of dorsal columns and corticospinal tract) Psychiatric Irritability, personality change Mild memory impairment, dementia [aafp.org]

  These were associated with mild weakness of the hands and feet, insomnia, irritability and constipation. There were no urinary symptoms, paralysis, gait disturbances, tremors, jaundice, limb swelling, changes in skin colour, or delusion. [bmcresnotes.biomedcentral.com]

• Stupor

  […] glossitis (3) stomatitis (4) pallor (5) loss of appetite with weight loss (6) mild jaundice (7) loss of central vision Psychiatric findings may include: (1) confusion (2) neurosis (3) delusions and/or hallucinations (4) memory loss (5) dementia (6) stupor [sites.google.com]

Although their clinical settings differ considerably, no hematologic finding can distinguish between the 2 conditions; specific testing is necessary (see Workup). [emedicine.medscape.com]

The pre-operative workup of these patients, therefore, should include cobalamin tests or flow cytometry, and deficiency should be fully resolved before surgery. [elsevier.es]

• Macrocytosis

  A diagnosis of vitamin B12 deficiency related peripheral neuropathy was made based on her symptoms, ovalo-macrocytosis and hyper-segmented neutrophils on peripheral blood smear. [bmcresnotes.biomedcentral.com]

  Macrocytosis for example is not specific to a vitamin B deficiency in children and also anaemia is not always present – as was previously assumed. [stichtingb12tekort.nl]

  […] but do not manifest typical megaloblastic morphology. ü Hypothyroidism is also associated with mild macrocytosis. [sites.google.com]

  The expected findings of very low serum cobalamin levels, anemia, and macrocytosis are often lacking. Arch Int Med 148, 1712-1714. 11) Carmel R., Green R., Rosenblatt D.S. and Watkins D. (2003a). Update on cobalamin, folate, and homocysteine. [myprotein.it]

  LFTs, TFTs and protein electrophoresis may help in the differential diagnosis of macrocytosis. Vitamin B12: Serum vitamin B12 is currently the standard initial routine diagnostic test. [patient.info]

• Macrocytic Anemia

  Complete blood count revealed severe macrocytic anemia (hemoglobin, 2.8 g/dL; mean corpuscular volume, 117 fL), thrombocytopenia (platelets, 117 × 10 9/L), and normal white blood cell count (13.6 × 10 9/L). [imagebank.hematology.org]

  It is a common cause of macrocytic (megaloblastic) anemia and, in advanced cases, pancytopenia. [sites.google.com]

  Entrez Gene IDs 6948 (Human); 21452 (Mouse); 64365 (Rat) Alternate Names D22S676; D22S750; macrocytic anemia; TC; TC-2; TC2II; TCII; TCN2; Transcobalamin II; transcobalamin II; macrocytic anemia; transcobalamin IITC II; transcobalamin-2; Vitamin B12-binding [rndsystems.com]

  References: [2] [4] Diagnostics Hematological findings Signs of megaloblastic anemia ↓ Hb ↑ MCV ( macrocytic ), ↑ MCH ( hyperchromic ) Hypersegmented neutrophils (lobe count ≥ 4 ) ↓ Reticulocytes, ↑ iron Frequently thrombocytopenia and leukopenia (possibly [amboss.com]

  The megaloblastic effect is characterized by an aregenerative macrocytic anemia with nuclear dysmaturity, where the nucleus appears immature relative to the cytoplasm because of impaired DNA synthesis. See image below. [emedicine.medscape.com]

However, neurologic disorders can be produced subsequently by improper treatment. [ncbi.nlm.nih.gov]

Oral treatment or treatment with cyanocobalamin instead of hydroxocobalamin may result in poorer outcomes. [orpha.net]

Has a currently accepted medical use in treatment in the United States or a currently accepted medical use with severe restrictions. [drugs.com]

CLOSE Medical Disclaimer The medical information on this site is provided as an information resource only, and is not to be used or relied on for any diagnostic or treatment purposes. [diseaseinfosearch.org]

Prognosis TC is a severe, life-threatening and rapidly progressing disease. Treatment, started early, is highly effective and reverses the clinical and hematological manifestations of the disease. [orpha.net]

People with pernicious anaemia are at increased risk of developing gastric cancer. [ 11 ] Prognosis Before the advent of treatment with B12, the disease was fatal. Hence the name 'pernicious'. [patient.info]

Etiology TC is caused by mutations in the TCN2 gene (22q12.2) which encodes transcobalamin, a transporter of cobalamin (vitamin B12). [orpha.net]

Causes The etiological factors leading to a deficiency of vitamin B12 may be due to deficit of the vitamin in the diet, impaired absorption of the vitamin because of malabsorption syndromes, and various miscellaneous gastrointestinal pathologies. [news-medical.net]

Etiology Malabsorption ↓ Intrinsic factor Pernicious anemia : most common cause of vitamin B 12 deficiency Atrophic gastritis (e.g., secondary to H. pylori infection) Gastrectomy ↓ Reduced uptake of IF- vitamin B 12 complex : e.g., Crohn's disease ;, [amboss.com]

Causes of Vitamin B 12 Deficiency States Once vitamin B 12 deficiency is confirmed, a search for the etiology should be initiated. [aafp.org]

Other less common causes include the use of metabolic inhibitors such as methotrexate and 6-mercaptopurine and certain rare inborn errors such as thiamine-responsive megaloblastic anemia, [1, 2] Lesch-Nyhan syndrome, and hereditary orotic aciduria (see Etiology [emedicine.medscape.com]

Summary Epidemiology To date, more than 40 cases of TC have been described in the literature. Clinical description TC typically manifests in the first few months of life. [orpha.net]

Genatlas disease for TCN2 Gene anemia,megalobastic,severe with thrombocytopenia and neutropenia,methylmalonic acidemia and homocystinuria Relevant External Links for TCN2 Genetic Association Database (GAD) TCN2 Human Genome Epidemiology (HuGE) Navigator [genecards.org]

Various biologic data and the epidemiologic evidence suggest that homocysteine itself is the cause, rather than an epiphenomenon, of arteriosclerosis [ 4 ]. [omicsonline.org]

Epidemiology [ 1 ] The incidence of pernicious anaemia in the UK population is estimated to lie between 1-5/100,000 per annum. [ 3 ] The disease occurs in all races. [patient.info]

Nathan and Oski’s is the only comprehensive product on the market that relates pathophysiology in such depth to hematologic and oncologic diseases affecting children. [books.google.com]

[…] surgical resection of the ileum Malnutrition ; : e.g., chronic alcoholism ;, anorexia nervosa, or strict vegan diets Increased demand : e.g., during pregnancy, breastfeeding, fish tapeworm ( Diphyllobothrium latum ) infections, and leukemia References: [1] Pathophysiology [amboss.com]

Biochemistry and Pathophysiology. Babior B.M., Ed., John Wiley & Sons, Inc., New York, pp. 287-333. 22) Okada, N.; Hadioetomo, P.S.; Nikkuni, S.; Katoh, K.; Ohta, T. Vitamin B12 content of fermented foods in the tropics. Rept. Nalt. Food Res. [myprotein.it]

For the reasons stated above, tetrahydrofolate cannot occur without cobalamin, and without tetrahydrofolate, neither methylenetetrahydrofolate nor its product, thymidylate, can occur. 23,24 Pathophysiology of megaloblastic anemia The pathophysiology of [elsevier.es]

Vitamin B 12 treatment must be continued for life unless the pathophysiologic mechanism for the deficiency is corrected. Infants of vegan mothers should receive supplemental vitamin B 12 from birth. [merckmanuals.com]

Early vitamin B12 therapy may prevent irreversible neurologic damage. [ncbi.nlm.nih.gov]

It also prevents accumulation of homocysteine. [orpha.net]

Prevention of Vitamin B 12 Deficiency Vitamin B 12 insufficiency can be prevented either by adherence to a diet that is sufficient in vitamin B 12 (see link), by the use of supplements, by injection of vitamin B 12 or via topical administration of vitamin [vitaminb12deficiency.net.au]

Early diagnosis and treatment is critical to prevent neurologic injury, disability, poor outcomes, and premature death. [pharmacytimes.com]

The literature is extensively reviewed, and the importance of early diagnosis to prevent neurological dysfunction is stressed. [link.springer.com]