A Young Man's Mystery Illness: How Vitamin B12 Deficiency Caused Severe Fatigue and Blood Abnormalities

Table of Contents

• Background: The Medical Mystery
• Case Presentation: The Patient's Story
• Initial Examination and Test Results
• The Diagnostic Process
• Differential Diagnosis: What Else It Could Have Been
• Final Diagnosis and Confirming Tests
• Clinical Implications for Patients
• Limitations of This Case Study
• Recommendations for Patients
• Source Information

Background: The Medical Mystery

This case from Massachusetts General Hospital demonstrates how vitamin deficiencies can sometimes present with dramatic and concerning symptoms that mimic more serious conditions. The patient's story highlights the importance of thorough diagnostic evaluation even when symptoms seem to point toward catastrophic illnesses.

Vitamin B12 deficiency affects approximately 6% of adults under 60 in the United States, with prevalence increasing with age. Despite being common, it can be overlooked when patients present with severe symptoms that suggest more acute medical emergencies.

Case Presentation: The Patient's Story

A 21-year-old man arrived at the hospital during summer months with concerning symptoms that had developed over four weeks. He had been completely healthy until experiencing nausea and vomiting that lasted one day, followed by persistent fatigue.

Two weeks before hospitalization, he developed additional symptoms including lightheadedness when changing positions and night sweats. His fatigue continued worsening until the morning of admission, when he experienced lightheadedness even while lying down, prompting his visit to the emergency department.

The patient worked as a carpenter with minimal outdoor exposure. He lived with family and had pets including two cats and a dog. He took no medications, didn't smoke or use alcohol or drugs, and had only one relevant family history detail—his maternal grandmother had lymphoma.

Initial Examination and Test Results

At the first hospital, doctors recorded vital signs showing a rapid heart rate of 121 beats per minute (normal is 60-100) and pale inner eyelids suggesting anemia. His initial blood tests revealed three critical abnormalities:

• Severe anemia: Hemoglobin of 5.1 g/dL (normal 14.0-18.0)
• Low white blood cells: 1,900 cells/μL (normal 4,800-10,800)
• Low platelets: 125,000 platelets/μL (normal 150,000-400,000)

Most strikingly, his lactate dehydrogenase (LDH)—a marker of cell damage—was extremely elevated at >2,500 U/L (normal 135-225). He received a blood transfusion and was transferred to Massachusetts General Hospital for specialized care.

At Mass General, his vital signs had improved with a heart rate of 89 beats per minute. Doctors noted areas of skin depigmentation (loss of color) near his elbows, fingers, and feet—a finding that would later prove important. His physical examination was otherwise normal.

The Diagnostic Process

Medical teams conducted extensive testing to determine the cause of his symptoms. His blood smear showed abnormal red blood cells including:

• Macroovalocytes (abnormally large oval-shaped red cells)
• Dacrocytes (teardrop-shaped cells)
• Neutrophils with increased segmentation (6 or more nuclear lobes)
• Some cells with basophilic stippling (abnormal blue speckling)

An abdominal ultrasound revealed mild spleen enlargement at 15.8 cm (normal <14.1 cm for his height and sex). Doctors performed numerous tests to rule out infections including Lyme disease, HIV, COVID-19, Epstein-Barr virus, cytomegalovirus, and parvovirus—all returned negative.

Differential Diagnosis: What Else It Could Have Been

The medical team considered multiple possible explanations for his severe symptoms:

Congenital diseases: Genetic conditions like GATA2 deficiency or Fanconi anemia were considered but deemed unlikely due to the rapid symptom onset (4 weeks versus years) and extremely high LDH level.

Infections: Various viral and bacterial infections were tested, but none typically cause such dramatically elevated LDH (nearly 3000 U/L) alongside macrocytic anemia.

Cancers: Leukemia or lymphoma were serious considerations given night sweats and family history, but preserved platelet and reticulocyte counts suggested bone marrow wasn't fully infiltrated by cancer cells.

Autoimmune disorders: Conditions like lupus or hemophagocytic lymphohistiocytosis were possible but lacked supporting evidence like fever or elevated ferritin.

Hemolytic anemia: The team ruled out conditions where the body destroys its own red cells because the reticulocyte response was too low given the degree of anemia and LDH elevation.

The diagnostic approach involved analyzing "scaling functions"—how different lab values related to each other in magnitude. The extremely high LDH (marker of cell damage) alongside relatively modest bilirubin elevation and low reticulocyte response created a pattern characteristic of vitamin B12 deficiency.

Final Diagnosis and Confirming Tests

The medical team ultimately diagnosed severe vitamin B12 deficiency. Confirmatory tests revealed:

• Vitamin B12 level: <150 pg/mL (severely deficient, normal >231 pg/mL)
• Methylmalonic acid: 1.00 nmol/mL (elevated, normal <0.40)
• Homocysteine: 21.5 μmol/L (elevated, normal 0-14.2)
• Folate level: 4.9 ng/mL (low normal, >4.7 considered adequate)

A bone marrow biopsy showed normocellularity with left-shifted erythroid hyperplasia—meaning his bone marrow was producing red blood cells that weren't maturing properly, characteristic of B12 deficiency.

The skin depigmentation noted earlier provided an important clue, as vitiligo (autoimmune skin depigmentation) is associated with pernicious anemia—an autoimmune condition that causes B12 deficiency.

Clinical Implications for Patients

This case demonstrates several important clinical insights about vitamin B12 deficiency:

Severe B12 deficiency can develop relatively quickly in some cases, contrary to the traditional teaching that depletion takes years. The hematologic (blood) and neurologic symptoms can occur independently—this patient had severe blood abnormalities without obvious nerve damage symptoms.

Laboratory patterns are crucial for diagnosis. The combination of extremely high LDH, modest bilirubin elevation, low reticulocyte response, and macrocytic anemia creates a distinctive pattern that experts can recognize.

Skin findings like vitiligo can provide diagnostic clues for associated autoimmune conditions that might cause B12 malabsorption.

Limitations of This Case Study

As a single case report, this presentation represents just one patient's experience. The rapid onset of severe symptoms might not be typical for most B12 deficiency cases.

The exact cause of this patient's B12 deficiency wasn't fully determined, though pernicious anemia (autoimmune condition) was suspected based on the vitiligo association. Not all patients will have such clear associated findings.

The dramatic lab abnormalities might lead to overtesting for more serious conditions before considering nutritional deficiencies, potentially delaying diagnosis in some cases.

Recommendations for Patients

If you experience persistent fatigue, lightheadedness, or night sweats:

1. Seek medical evaluation rather than assuming symptoms are just from stress or lack of sleep
2. Request basic blood tests including complete blood count (CBC) and possibly vitamin levels if deficiency is suspected
3. Note any skin changes like depigmentation to discuss with your doctor
4. Don't overlook nutritional causes even when symptoms seem severe—deficiencies can cause dramatic presentations
5. Follow up on abnormal results even if you start feeling better, as underlying conditions need treatment

For patients with confirmed B12 deficiency, treatment typically involves B12 injections or high-dose oral supplements with regular monitoring to ensure levels normalize and symptoms resolve.

Source Information

Original Article Title: Case 6-2024: A 21-Year-Old Man with Fatigue and Night Sweats

Authors: Jonathan C.T. Carlson, M.D., Madeleine M. Sertic, M.B., B.Ch., and Maria Y. Chen, M.D., Ph.D.

Publication: The New England Journal of Medicine, February 22, 2024; 390:747-56

DOI: 10.1056/NEJMcpc2309498

This patient-friendly article is based on peer-reviewed research from Massachusetts General Hospital's Case Records.