Vitamin B12 Deficiency (Cobalamin)


Article Author:
Alex Ankar


Article Editor:
Anil Kumar


Editors In Chief:
Dustin Constant
Donald Kushner


Managing Editors:
Avais Raja
Orawan Chaigasame
Carrie Smith
Abdul Waheed
Khalid Alsayouri
Kyle Blair
Trevor Nezwek
Radia Jamil
Erin Hughes
Patrick Le
Anoosh Zafar Gondal
Saad Nazir
William Gossman
Hassam Zulfiqar
Navid Mahabadi
Hussain Sajjad
Steve Bhimji
Muhammad Hashmi
John Shell
Matthew Varacallo
Heba Mahdy
Ahmad Malik
Abbey Smiley
Sarosh Vaqar
Mark Pellegrini
James Hughes
Beata Beatty
Daniyal Ameen
Altif Muneeb
Beenish Sohail
Nazia Sadiq
Hajira Basit
Phillip Hynes
Komal Shaheen
Sandeep Sekhon


Updated:
1/11/2019 6:07:25 PM

Introduction

Vitamin B12 (Cobalamin) is a water-soluble vitamin that is derived from animal products such as red meat, dairy, and eggs. Intrinsic factor is a glycoprotein that is produced by parietal cells in the stomach and necessary for the absorption of B12 in the terminal ileum. Once absorbed, B12 is used as a cofactor for enzymes that are involved in the synthesis of DNA, fatty acids, and myelin. As a result, a B12 deficiency can lead to hematologic and neurologic symptoms. B12 is stored in excess in the liver; however, in cases in which B12 cannot be absorbed for a prolonged period (e.g., dietary insufficiency, malabsorption, lack of intrinsic factor), hepatic stores are depleted, and deficiency occurs.[1][2][3]

Etiology

Vitamin B12 deficiency has 3 primary etiologies:

  1. Autoimmune: Pernicious anemia is an autoimmune condition in which antibodies to intrinsic factor are produced. Anti-intrinsic factor antibodies bind to and inhibit the effects of intrinsic factor, resulting in an inability of B12 to be absorbed by the terminal ileum. 
  2. Malabsorption: Parietal cells in the stomach produce intrinsic factor; therefore, any patient with a history of gastric bypass surgery may be at risk for developing a B12 deficiency because their new alimentary pathway bypasses the site of intrinsic factor production. In patients with normal intrinsic factor production, any damage to the terminal ileum, such as surgical resection due to Crohn disease, will impair the absorption of B12 and lead to a deficiency. Other damage to the small intestine, such as inflammation from Celiac disease or infection with the tapeworm Diphyllobothrium latum, may also result in a B12 deficiency.
  3. Dietary Insufficiency: Vitamin B12 is stored in excess in the liver; however, patients who have followed a strict vegan diet for approximately three years may develop a B12 deficiency from a lack of dietary intake.

Epidemiology

The epidemiology of vitamin B12 deficiency varies based on the etiology. In the general population, some studies have shown that among patients with anemia, approximately 1% to 2% is due to B12 deficiency. Other studies have shown that among patients with clinical macrocytosis (defined as an MCV > 100), 18% to 20% were due to B12 deficiency. Vitamin B12 deficiency is more common in the elderly, regardless of the cause.

B12 deficiency due to pernicious anemia is more common in people of Northern European ancestry. The incidence of pernicious anemia is lower in people of African descent or people from other areas of Europe.[4][5]

Pathophysiology

In healthy patients, dietary vitamin B12 binds to a protein called R-factor, which is secreted from salivary glands. Once the complex arrives at the small intestine, B12 is cleaved from R-factor by pancreatic enzymes, allowing it to bind to a glycoprotein called intrinsic factor, which is secreted by gastric parietal cells. The newly formed complex of B12 and intrinsic factor can then bind to receptors on the ileum, which allows for absorption of B12. Once absorbed, B12 is involved in metabolic pathways important in both neurologic and hematologic functions. If B12 cannot be absorbed, regardless of the etiology, many impairments may occur.

Vitamin B12 is a cofactor for the enzyme methionine synthase, which is used in the conversion of homocysteine to methionine. As a byproduct of this reaction, methyl-THF is converted to THF, which is converted to intermediates used in the synthesis of pyrimidine bases of DNA. In B12 deficiency, homocysteine cannot be converted to methionine, and thus, methyl-THF cannot be converted to THF. As a result, homocysteine levels accumulate, and pyrimidine bases cannot be formed, slowing down DNA synthesis and causing megaloblastic anemia. The anemia then leads to symptoms such as fatigue and pallor that are commonly seen in patients with B12 deficiency. The impaired DNA synthesis causes problems for other rapidly proliferating cell lines, such as PMNs. Thus, B12 deficiency characteristically results in the formation of hypersegmented neutrophils.

Vitamin B12 is also used as a cofactor for the enzyme methylmalonyl-CoA mutase, which converts methylmalonyl-CoA to succinyl-CoA. In patients with B12 deficiency, methylmalonic acid (MMA) levels will accumulate, as it cannot be converted to succinyl-CoA. It is hypothesized that elevated levels of MMA, along with elevated levels of homocysteine, contribute to myelin damage, accounting for the neurologic deficits, such as neuropathy and ataxia, seen in these patients. The damage to the myelin results in a condition known as subacute combined degeneration of the spinal cord (SCDSC). This condition affects various parts of the spinal cord, including the dorsal columns, the lateral corticospinal tracts, and the spinocerebellar tracts, resulting in a loss of proprioception, ataxia, the development of peripheral neuropathy, and dementia.[6][7]

History and Physical

A thorough evaluation of vitamin B12 deficiency should include a complete history and physical with increased emphasis on gastrointestinal (GI) and neurologic findings. B12 deficiency manifests as macrocytic anemia, and thus, the presenting symptoms often include signs of anemia, such as fatigue and pallor. Due to the increased hemolysis caused by impaired red blood cell formation, jaundice may also be a presenting symptom. Therefore, a thorough dermatologic exam may also be helpful. Other presenting complaints may include peripheral neuropathy, glossitis, diarrhea, headaches, and neuropsychiatric disturbances.

When obtaining a complete GI history, it is important to look for a past medical history of the Celiac disease or Crohn disease. Any surgical history of gastrectomy or bowel resection, especially resection of the ileum, should increase suspicion for B12 deficiency. In addition, a dietary history may reveal that a patient has switched to a strict vegan diet within the last few years, which would also increase suspicion for B12 deficiency.

In more severe cases, the disease process can progress to involve the nervous system. As mentioned above, SCDSC can result from B12 deficiency, causing damage to various segments of the spinal cord. A complete neurologic exam should evaluate for dementia, peripheral neuropathy, ataxia, and a loss of proprioception. A mental status exam may also be useful to evaluate any neuropsychiatric changes.

Evaluation

In patients with suspected B12 deficiency, initial lab tests should include a complete blood count (CBC) with a peripheral smear and serum B12 and folate levels. In cases where the diagnosis is still unclear after initial testing, other lab tests, such as MMA and homocysteine levels, are available. 

In patients who are deficient in B12, the CBC would show anemia, which manifests as a decrease in both hemoglobin and hematocrit. In addition, the mean corpuscular volume (MCV), which measures the size of red blood cells, would be increased to a level greater than 100. This is consistent with a diagnosis of macrocytic anemia. A peripheral blood smear would show hypersegmented neutrophils, with a portion of the neutrophils having greater than or equal to five lobes. 

Serum B12 and folate levels also should be obtained. Folic acid deficiency also presents as macrocytic anemia and is often confused with B12 deficiency. Ordering serum levels of both B12 and folate can help differentiate between the two disease processes. A serum B12 above 300 pg/mL is interpreted as normal. Patients with B12 levels between 200 and 300 pg/mL are considered borderline, and further enzymatic testing may be helpful in diagnosis. Patients with B12 levels below 200 pg/mL are considered deficient. However, a low serum B12 level does not determine the etiology of the deficiency. If the etiology is uncertain, further testing should be done to investigate.

In patients with borderline B12 levels (200 to 300 pg/mL), further enzymatic testing should be performed. As described, B12 deficiency results in the accumulation of MMA and homocysteine. Thus, serum levels of MMA and homocysteine both should be elevated in cases of B12 deficiency. These lab values also can help to distinguish B12 deficiency from folate deficiency, in which homocysteine levels are elevated, but MMA levels are normal. 

After a B12 deficiency confirmation, the etiology must be addressed. Often, a surgical history including a gastrectomy, resection of the terminal ileum, or gastric bypass will be the cause. If there is no pertinent surgical history, an appropriate GI workup for causes of malabsorption, such as Crohn or Celiac disease should be performed. In other cases, a history of adherence to a strict vegan diet may be the source. If both the GI and dietary workup is negative, then the cause is likely autoimmune. Blood tests for serum levels of anti-intrinsic factor antibodies may lead to the diagnosis of pernicious anemia. Classically, a test known as the Schilling test was used to diagnose pernicious anemia; however, this test is no longer performed. It involved having the patient orally ingest radiolabeled B12. If the patient excreted the radiolabeled B12 in the urine, it indicated normal B12 absorption. A problem with B12 absorption prevents radiolabeled B12 excretion into the urine, indicating a cause of malabsorption or pernicious anemia.[8][9][10]

Treatment / Management

Treatment of vitamin B12 deficiency involves repletion with B12. However, depending on the etiology of the deficiency, the duration and route of treatment vary. In patients who are deficient due to a strict vegan diet, an oral supplement of B12 is adequate for repletion.

In patients with a deficiency in intrinsic factor, either due to pernicious anemia or gastric bypass surgery, a parenteral dose of B12 is recommended, as oral B12 will not be fully absorbed due to the lack of intrinsic factor. A dose of 1000 mcg of B12 via the intramuscular route is recommended once a month. In newly diagnosed patients, 1000 mcg of B12 is given intramuscularly once a week for four weeks to replenish stores before switching to once-monthly dosing. Studies have shown that at doses high enough to fully saturate intestinal B12 receptors, oral B12 is also effective, despite a lack of intrinsic factor.

In anyone at risk of developing a B12 deficiency, such as patients with Crohn disease or Celiac disease, routine monitoring of B12 should be performed. If the severity of the disease worsens and B12 levels begin to decline, treatment is then started. However, prophylactic treatment before B12 levels fall is not indicated.[11][12][13]

Differential Diagnosis

Complications

Enhancing Healthcare Team Outcomes

Vitamin B12 deficiency is a serious disorder, which if not treated can lead to severe neurological symptoms. The ideal way to manage the disorder is with an interprofessional team that includes an internist, gastroenterologist, neurologist, surgeon, pharmacist, and nurse. The primary focus today is to try to prevent the disorder in the first place. The nurse and pharmacist can help educate the patient that there is an increased risk among family members, who should be screened for the disorder. Further, any patient who has undergone gastric resection surgery is also at risk for vitamin B12 deficiency and should be regularly tested. The pharmacist should also recommend testing in patients treated with metformin and proton pump inhibitors. Finally, vitamin B12 deficiency is common in seniors because of poor nutrition, dementia, rigid vegetarian diet or lack of access to care. These individuals should be proactively screened for vitamin B12 deficiency. Once treated, the individuals should be followed by a visiting home care nurse to make sure that the neurological symptoms are improving.[14]

Outcomes

For patients who are promptly treated with vitamin B12, the neurological symptoms of Subacute combined degeneration partially resolve, and the progression may stop. In general, younger patients have better outcomes compared to older individuals. The best response is obtained in people with absence of severe neurological deficits. In addition, in patients with an MRI showing mild cord swelling or less than 7 spinal segment involvement, the prognosis is good. However, the clinical improvement may take months or even years. [15][16] (Level V)


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Vitamin B12 Deficiency (Cobalamin) - Questions

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In an individual infected with diphyllobothriasis, which of the following deficiencies will be observed long term?



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If malabsorption of vitamin B12 is corrected with intrinsic factor administration, then the patient most likely has?



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Which of the following is not a cause of vitamin B12 deficiency?



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A 48-year-old female complains of anorexia, numbness and tingling of the feet, dyspepsia, and weakness of the legs. On exam she has a smooth sore tongue, numbness, and megaloblastic anemia. She most likely has a deficiency of which of the following?



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A 70-year-old woman has been profoundly fatigued for several weeks. Physical examination shows pallor, poor short term memory, and decreased leg vibratory sense. An EKG shows ST depression but no Q waves. Hemoglobin is 4.2 g/dL, mean corpuscular volume is 104 mm3, white blood cell count is 4000 per mm, and platelet count is 50,000 per mm3. There is also hypersegmentation of neutrophils, basophilic stippling, marked anisocytosis, and poikilocytosis with some large oval erythrocytes. What is the metabolic response to this vitamin deficiency?



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A 60-year-old man is status post-gastrectomy for Zollinger-Ellison syndrome and is told he requires monthly intramuscular vitamin B12 injections for life. A loss of which of the following cell types is responsible for this requirement?



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A 64-year-old male patient presents to his physician's office with bilateral lower extremity paresthesias and ataxia. The physician orders a complete blood count (CBC), which reveals a megaloblastic anemia. Upon further exploration of this patient's surgical history, a history of which of the following procedures would most likely be expected given this patient's presentation?



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In a patient with vitamin B12 deficiency, one would expect to find which of the following?



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A patient has been complaining of decreased sensation in the lower extremities. Laboratory studies reveal a hemoglobin 9.8 g/dL, hematocrit 33.2%, and MCV 125 fL. Microscopic examination of peripheral blood smear shows red blood cells with macrocytosis and neutrophils with hypersegmentation of nuclei. Which of the following is the most likely deficiency?



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A 55-year-old patient has been complaining of decreased sensation in the lower extremities. Laboratory studies reveal a hemoglobin 9.8 g/dL, hematocrit 33.2%, and MCV 125 fL. Microscopic examination of peripheral blood smear shows red blood cells with macrocytosis and neutrophils with hypersegmentation of nuclei. Which of the following is most likely deficient?



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A 68-year-old woman has been profoundly fatigued for several months. Exam shows pallor, poor short-term memory, and decreased leg vibratory sense. EKG shows ST-depression. Hemoglobin is 4.1 g/dL, MCV 105 microm3, a white-cell count of 5000 per mm; and a platelet count of 55,000 per mm3. Also noted is hypersegmentation of neutrophils, basophilic stippling, marked anisocytosis, and poikilocytosis with some large oval erythrocytes. What is the metabolic response to this vitamin deficiency?



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A 55-year-old male presents to his physician's office for his annual follow up visit. He has complaints of fatigue for the last several months. His physician performs a complete blood count which reveals a macrocytic anemia. Further testing reveals a low serum B12 level. Which of the following would not be a symptom seen in this patient due to his newly-diagnosed vitamin deficiency?



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A 77-year-old female is seen for follow-up in her physician's office after a recent hospitalization for hepatic encephalopathy due to liver cirrhosis. She also has a history of celiac disease diagnosed at age 35. The patient is a chronic alcoholic and drinks 5 to 6 cans of beer a day. While in the hospital, the patient was found to have a macrocytic anemia on a routine complete blood count (CBC). Her physician suspects that this lab abnormality is either due to vitamin B12 or folate deficiency. If this patient's macrocytosis is due to B12 deficiency, which of the following metabolic changes would also be expected?



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A 50-year-old male presents to the clinic for his annual follow-up visit. He has a history of Crohn disease, which was complicated by a surgical resection of the terminal ileum five years ago. He received intramuscular injections of vitamin B12 monthly up until 18 months ago when he lost his job and missed many appointments. The physician finds that this patient has a positive Romberg test. This test likely indicates damage to which of the following neurological structures?



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A 47-year-old male is scheduled for a resection of his terminal ileum due to a flare-up of Crohn disease. At the initial surgical evaluation, the physician mentions that he will likely need monthly vitamin B12 injections for the rest of his life after this operation. The physician tells the patient that about symptoms that may occur if he does not take the B12 shots. Which of the following findings would not be a typical observation in a patient with a B12 deficiency?



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A 58-year-old male presents to his physician's office for his annual follow-up visit. His past medical history is notable for celiac disease diagnosed at age 24. He has no other significant past medical history. He complains of feeling fatigued for the last several months. He also complains of decreased feeling in his feet bilaterally. His physician orders a complete blood count (CBC), which reveals a decrease in hemoglobin and hematocrit. His physician suspects that this patient's anemia is due to a vitamin deficiency. What type of anemia would be expected in this patient?



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A 30-year-old male presents to his physician's office for his annual follow-up visit. He has no new medical issues, but he has felt more fatigued for the last several months. He has a history of celiac disease that was diagnosed 5 years ago. Routine lab work shows a macrocytic anemia. The physician suspects this is due to a deficiency in vitamin B12 and orders more lab tests. Which of the following metabolites would be elevated due to this patient's suspected vitamin B12 deficiency?



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A 38-year-old obese female presents to her physician's office for assistance with weight loss. She mentions to her physician that she is considering switching to a strict vegan diet for health reasons. The physician warns the patient that maintaining a strict vegan diet for several years could lead to a deficiency in vitamin B12. Which of the following symptoms would not be a typical presentation of vitamin B12 deficiency?



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A 32-year-old woman comes to the clinic for her annual follow-up visit. She has no new medical complaints and no significant past medical history. Her neighbor was recently diagnosed with vitamin B12 deficiency, and the patient would like to know whether or not she should take supplemental B12 to prevent the same thing from occurring to her. What is the most common cause of the vitamin deficiency seen in this patient's neighbor?



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A 59-year-old female presents to her physician's office for her annual follow-up visit. She has a past medical history of celiac disease and vitamin B12 deficiency. She eats a gluten-free diet and receives monthly B12 injections. She has no new medical problems at this visit. She asks her physician about potential complications of her vitamin deficiency. Which of the following can result from longstanding vitamin B12 deficiency?



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A 77-year-old female presents to her physician's office for her annual follow-up visit. She has a past medical history of hypertension and hyperlipidemia. She takes lisinopril and simvastatin. She has no new complaints at this medical visit, but she has felt fatigued for the last several months. Her routine lab work reveals a decreased hemoglobin, hematocrit, and an increased mean corpuscular volume. Further testing shows a low serum vitamin B12 level. Which of the following is not associated with a deficiency in this vitamin?



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A 42-year-old male presents to his physician for follow-up after surgical resection of his ileum due to a flare-up of his Crohn disease. He has no other medical problems and only takes mesalamine. His physician mentions that he will likely require monthly injections to prevent a deficiency of vitamin B12 after his recent surgery. If this patient develops a deficiency in B12, which of the following metabolites will be increased in his blood?



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A 62-year-old female patient is seen in the clinic for her annual follow-up visit. She has a past medical history of hypertension, hyperlipidemia, and depression. Her current medications include aspirin, simvastatin, lisinopril, and fluoxetine. She was diagnosed with celiac disease at age 28 and follows a gluten-free diet. She notes that she has felt increasingly fatigued over the last few months. She has also noticed a new-onset of numbness and tingling in her lower extremities, as well as problems with balance. Her physical exam was significant for a noted decrease in sensation to both pinprick and light touch of her bilateral lower feet. She was also found to have a positive Romberg test. A complete blood count (CBC) reveals a decrease in hemoglobin, a decrease in hematocrit, and an increased mean corpuscular volume (MCV). The physician suspects a vitamin deficiency as the cause of this patients neurological problems. Which of the following structures is most likely affected by this patient's suspected vitamin deficiency?



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A 58-year-old male comes to his physician's office with complaints of new-onset vision problems. He also complains of recent numbness and tingling in both of his feet as well as problems with balance. He has a history of celiac disease that was diagnosed at age 20. He follows a gluten-free diet and takes sertraline for problems with depression. The physician diagnoses the patient with a cecocentral scotoma, which he believes is likely due to a vitamin deficiency. Which of the following vitamins is most likely responsible for this patient's vision troubles?



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A 42-year-old female presents to the clinic for follow-up after being released from an alcohol detoxification program. Prior to admission to the program, she had consumed 6 to 7 beers daily for the past year. She has no other known medical conditions outside of depression controlled with fluoxetine. She notes that for the past year, she has had multiple episodes of bloating, cramping, and non-bloody diarrhea after most meals. A complete blood count (CBC) reveals a macrocytic anemia. Further lab tests reveal a normal folic acid level and a B12 level in the low-normal range. An increase in which of the following metabolites would confirm the suspected diagnosis in this patient?



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A 32-year-old patient who has recently moved to the United States from eastern Europe presents to the clinic with a chief complaint of fatigue. She has noted increased shortness of breath and fatigue over the past three months. She has no other complaints at this time. Her past medical history is significant for asthma treated with albuterol and eczema treated with a topical steroid cream. Her physical exam is significant for conjunctival pallor and a glossy tongue. Her heart sounds are normal, and her lungs are clear to auscultation bilaterally. A complete blood count (CBC) shows a macrocytic anemia with an MCV of 110 fL. The physician suspects an autoimmune etiology of this patient's symptoms. Autoantibodies to which of the following would likely be seen in this patient?



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A 45-year-old female presents to her physician's office for her annual follow-up. She has no new complaints and no significant past medical history. Her BMI is 34.0. She inquires about switching to a strict vegan diet to lose weight, but she has heard from various family members that it may lead to a vitamin B12 deficiency. Which is not true regarding short term B12 deficiency?



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A 28-year-old female has recently moved to the United States from Eastern Europe and presents to the clinic to establish care. She has a past medical history of anxiety and pernicious anemia. Her current medications include a daily multivitamin and sertraline. She has been receiving monthly injections of vitamin B12 ever since her diagnosis of pernicious anemia. The patient asks her physician about the necessity of taking supplemental B12. Which of the following symptoms could develop if this patient stops receiving her B12 injections?



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A 60-year-old male presents to his physician's office for his annual follow-up. He has a history of Crohn disease treated with mesalamine. He also has hypertension that is controlled with lisinopril, and hyperlipidemia that is controlled with pravastatin. He had a surgical resection of his terminal ileum 5 years ago due to a flare-up of his Crohn disease. A physical exam reveals a decrease in sensation to both pinprick and light touch bilaterally in his lower extremities. The physician suspects this patient's neuropathy is due to a deficiency in Vitamin B12. A deficiency in B12 would also lead to which of the following physical exam findings?



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A 38-year-old female presents to her physician's office after having gastric bypass surgery 2 weeks ago. The patient also has hyperlipidemia, hypertension, and type 2 diabetes mellitus. Her current medications include aspirin, simvastatin, lisinopril, and metformin. Her physician tells her that patients with a history of gastric bypass are at an increased risk for cobalamin deficiency. Which of the following findings do not occur with a deficiency of cobalamin?



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A 65-year-old woman with a past medical history of hypertension, gout, major depressive disorder, and Crohn disease presents to her physician's office with a several month history of fatigue with burning and tingling in both of her feet. She is currently taking lisinopril, allopurinol, sertraline, and mesalamine. 1 year ago, she underwent a surgical resection of her ileum due to an exacerbation of Crohn disease. She has not had a gout flare-up in the last 8 months. Two years ago, she completed a detox program for alcohol use disorder and has not used alcohol since. In the office, her blood pressure was 142/90 mmHg. Physical exam showed diffuse epigastric tenderness with no acute joint abnormalities. Sensation to light touch and pinprick were decreased bilaterally on the plantar surface of both feet. Lab data reveals anemia with an MCV of 102.3. Which event from this patient's history most likely explains her current neuropathic symptoms?



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Which of the following symptoms is most specific for vitamin B12 deficiency?



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A Northern European patient was diagnosed with vitamin B12 deficiency many years ago and refused to be treated. He now has dementia. Which disorder will this most resemble?



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A 93-year old female presents to the emergency department via emergency medical services from a nursing home with a two-week history of fatigue, confusion, shortness of breath, and malaise. She also has a past medical history of gastroesophageal reflux disease and achalasia with previous lower esophageal sphincter stretching three years ago. Upon review of the records from the nursing home facility, it is determined that the patient has been consuming a diet of primarily liquids and vegetables. She has refused to eat any protein in the form of meat for the past nine months. Physical exam reveals loss of sensation on the plantar surfaces of the feet bilaterally. She says that they started burning two months ago before she lost sensation. A CBC reveals hemoglobin of 8.4, hematocrit is 29%, and MCV of 118. Which nutritional deficiency is causing these symptoms?



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Vitamin B12 Deficiency (Cobalamin) - References

References

Layden AJ,Täse K,Finkelstein JL, Neglected tropical diseases and vitamin B12: a review of the current evidence. Transactions of the Royal Society of Tropical Medicine and Hygiene. 2018 Aug 28     [PubMed]
Fritz J,Walia C,Elkadri A,Pipkorn R,Dunn RK,Sieracki R,Goday PS,Cabrera JM, A Systematic Review of Micronutrient Deficiencies in Pediatric Inflammatory Bowel Disease. Inflammatory bowel diseases. 2018 Aug 21     [PubMed]
Miller JW, Proton Pump Inhibitors, H2-Receptor Antagonists, Metformin, and Vitamin B-12 Deficiency: Clinical Implications. Advances in nutrition (Bethesda, Md.). 2018 Jul 1     [PubMed]
Röhrig G,Gütgemann I,Kolb G,Leischker A, [Clinical hematological symptoms of vitamin B{sub}12{/sub} deficiency in old age : Summarized overview of this year's symposium of the Working Group     [PubMed]
Devi A,Rush E,Harper M,Venn B, Vitamin B12 Status of Various Ethnic Groups Living in New Zealand: An Analysis of the Adult Nutrition Survey 2008/2009. Nutrients. 2018 Feb 7     [PubMed]
Oo TH,Rojas-Hernandez CM, Challenging clinical presentations of pernicious anemia. Discovery medicine. 2017 Sep     [PubMed]
Cavalcoli F,Zilli A,Conte D,Massironi S, Micronutrient deficiencies in patients with chronic atrophic autoimmune gastritis: A review. World journal of gastroenterology. 2017 Jan 28     [PubMed]
Coskun M,Sevencan NO, The Evaluation of Ophthalmic Findings in Women Patients With Iron and Vitamin B12 Deficiency Anemia. Translational vision science     [PubMed]
Bhat DS,Gruca LL,Bennett CD,Katre P,Kurpad AV,Yajnik CS,Kalhan SC, Evaluation of tracer labelled methionine load test in vitamin B-12 deficient adolescent women. PloS one. 2018     [PubMed]
Guan B,Yang J,Chen Y,Yang W,Wang C, Nutritional Deficiencies in Chinese Patients Undergoing Gastric Bypass and Sleeve Gastrectomy: Prevalence and Predictors. Obesity surgery. 2018 May 12     [PubMed]
Bromage S,Ganmaa D,Rich-Edwards JW,Rosner B,Bater J,Fawzi WW, Projected effectiveness of mandatory industrial fortification of wheat flour, milk, and edible oil with multiple micronutrients among Mongolian adults. PloS one. 2018     [PubMed]
Homan J,Schijns W,Aarts EO,Janssen IMC,Berends FJ,de Boer H, Treatment of Vitamin and Mineral Deficiencies After Biliopancreatic Diversion With or Without Duodenal Switch: a Major Challenge. Obesity surgery. 2018 Jan     [PubMed]
Freedberg DE,Kim LS,Yang YX, The Risks and Benefits of Long-term Use of Proton Pump Inhibitors: Expert Review and Best Practice Advice From the American Gastroenterological Association. Gastroenterology. 2017 Mar     [PubMed]
Ziegler O,Sirveaux MA,Brunaud L,Reibel N,Quilliot D, Medical follow up after bariatric surgery: nutritional and drug issues. General recommendations for the prevention and treatment of nutritional deficiencies. Diabetes     [PubMed]
Cham G,Davis N,Strivens E,Traves A,Manypeney G,Gunnarsson R, Factors correlating to the propensity of general practitioners to substitute borderline vitamin B12 deficiency. Scandinavian journal of primary health care. 2018 Jun 22     [PubMed]
Watson J,Lee M,Garcia-Casal MN, Consequences of Inadequate Intakes of Vitamin A, Vitamin B{sub}12{/sub}, Vitamin D, Calcium, Iron, and Folate in Older Persons. Current geriatrics reports. 2018     [PubMed]

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