Vitamin B12 deficiency

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Vitamin B12 deficiency

Hematological system

Hematological system

Hematological system

Hematological system


Vitamin B12 deficiency


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Vitamin B12 deficiency

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A 32-year-old woman comes to her primary care physician with worsening depression and frequent falls. She has had difficulty sleeping at night and has frequently been stumbling over herself while walking. The patient states “my legs feel numb all the time.” Her partner, who is also present during the visit, states that the patient has not been herself lately and has been eating less since her mother passed away. Past medical history is notable for Crohn disease, depression, and Graves disease. She drinks alcohol socially, occasionally smokes marijuana, and adheres to a vegan diet. Her temperature is 37.0°C (98.6°F), pulse is 67/min, respirations are 14/min, blood pressure is 110/74 mmHg, and O2 saturation is 98% on room air. Physical examination is notable for a sad affect, an ataxic gait, as well as paresthesias and hyperactive deep tendon reflexes in the lower extremities bilaterally. Laboratory testing reveals the following results:  

 Laboratory Value  Result 
 Hemoglobin  10.5 g/dL 
 Leukocyte count  1,000/mm3 
 Platelet count    90,000/mm3 
 Mean corpuscular volume  115 μm3 

Which of the following is the most likely etiology of this patient’s symptoms? 

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Vitamin B12 deficiency refers to low levels of Vitamin B12 in the body.

This can lead to a variety of problems ranging from anemia to soreness of the tongue and neurological dysfunction.

Vitamin B12, also known as cobalamin, is a complex organometallic compound found in animal and dairy products like meat, eggs or milk.

Dairy and animal products are broken down in the stomach by pepsin, which is the active form of a gastric enzyme called pepsinogen, to release B12.

Then, a protein made by parietal cells in the stomach, called intrinsic factor, can bind to B12, and the B12-intrinsic factor complex passes into the intestines.

When the complex reaches the terminal ileum, the enterocytes, which are the special cells lining the intestines, recognize intrinsic factor and absorb the whole complex.

Inside the enterocytes, intrinsic factor gets removed and a special protein called transcobalamin-II binds the free B12 and transports it into the blood and from there, to various target tissues.

Some of the transcobalamin-B12 complex gets to the liver, where B12 can be stored for several years.

B12 is used to synthesize DNA precursors, which is essential for cell division.

First, vitamin B12 accepts a methyl group from methyl tetrahydrofolate or methyl-THF, making methylcobalamin and free tetrahydrofolate, or THF in the process.

THF then gets an extra “methylene” group from serine, an amino acid found within the cells.

THF quickly transfers the methylene to a nucleotide called deoxyuridine monophosphate, or d-UMP for short.

As a result, d-UMP becomes d-TMP or deoxythymidine monophosphate, which can then be converted to thymidine, one of the nucleotides used to build DNA.

Going back, the methylcobalamin that was formed along with THF transfers its methyl group to homocysteine and converts it into an essential amino acid called methionine, thus lowering the levels of homocysteine in the body, too much of which can be harmful.


Vitamin B12 deficiency is a clinical condition caused by insufficient levels of Vitamin B12 in the body, which hinders cell division and causes an excess of homocysteine and methylmalonic acid. This can result in macrocytic megaloblastic anemia, characterized by pallor, dyspnea, and fatigue; glossitis or inflammation of the tongue, resulting in swelling and tenderness, dysphonia, and dysphagia; and myelin damage, which may lead to changes in reflexes, decreased muscle function, memory impairment, and, in rare cases, psychosis. Diagnosis of B12 deficiency can be confirmed by conducting a peripheral blood smear, measuring serum levels of vitamin B12, as well as serum homocysteine and methylmalonic acid levels. B12 deficiency is effectively treated with oral supplements or intramuscular injections of vitamin B12.


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