Vitamin B12 deficiency
Biochemistry and nutrition
AssessmentsVitamin B12 deficiency
Vitamin B12 deficiency
USMLE® Step 1 style questions USMLE
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:
|Mean corpuscular volume||115 μm3|
Which of the following is the most likely etiology of this patient’s symptoms?
Vitamin B12 deficiency exam links
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.
Alternatively, B12 can be used by the mitochondria in another active form called “adenosylcobalamin” - which is basically B12 with an adenosyl group clinging to it! Adenosylcobalamin acts as a coenzyme for methylmalonyl coenzyme A mutase, an enzyme which converts methylmalonyl co-A into succinyl co-A.
This helps reduce the levels of methylmalonic acid, which can also be harmful if it builds up.
So in short, the consequences of B12 deficiency are that cell division is impaired, and there’s too much homocysteine and methylmalonic acid in the body.
When cell division grinds to a halt, rapidly dividing cells in the bone marrow are affected, like red and white blood cells, as well as platelet precursors.
Inside the bone marrow, red blood cell precursors are normally big and plump, and they undergo a series of cell divisions which results in smaller mature RBCs.
Now with B12 deficiency, at first, the bone marrow pumps out larger, but still mature RBCs called macrocytes.
These RBCs are destroyed in the spleen, which causes a decrease in the total RBC count, or anemia.
In response, the bone marrow compensates by releasing abnormally developed RBC precursors, called megaloblasts, into the blood, and the final result is macrocytic, megaloblastic anemia.
B12 deficiency also affects white blood cell production - so the bone marrow starts releasing large, immature neutrophils, with hypersegmented nuclei - meaning their nucleus has more than 5 lobes.
Finally, severe B12 deficiency may also decrease the production of megakaryocytes, which are the platelet precursors in the bone marrow.
So when all 3 blood cell lines are affected, this results in pancytopenia, which is when red blood cell, white blood cell and platelet count is low.
And folate deficiency also decreases white blood cell, red blood cell, and megakaryocytes production in the bone marrow, also resulting in pancytopenia.
Other rapidly dividing cells are mucosal epithelial cells, especially those of the tongue mucosa.
Have you ever noticed how fast your tongue heals if you accidentally bite it?
That’s because old epithelial cells are replaced with new ones in the blink of an eye!
Okay, not literally that fast, but it is pretty quick.
In B12 deficiency, old epithelial cells aren’t replaced, and this slows down the healing of normal wear and tear of the tongue, which ultimately leads to inflammation of the tongue, known as glossitis.
Next, when homocysteine builds up in the body, some of it is excreted in the urine leading to homocystinuria.
They also build up in the blood, where they bind to the endothelial cells lining blood vessels, causing them to secrete molecules called proinflammatory cytokines.
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.