A 60-year-old man comes to your office complaining that “I’ve been feeling really tired lately
and get out of breath just walking around the house.” He also tells you that “my feet always
go to sleep on me; they feel like pins and needles.” After some discussion, he informs you
that his tongue feels “kind of big and beefy” and that he has been falling down a lot. When
questioned about his alcohol consumption, he emphatically denies being an alcoholic but
admits that “I do like to have a glass of whiskey every day.” In addition, you noticed that he
walked very stiffly as he came into the examining room. What is the most likely diagnosis?
• Beriberi, diabetes, folate deficiency due to alcoholism or poor diet, lead poisoning, uremia
Relevant Physical Examination Findings
• Conjunctiva and nail beds are pale.
• Skin is colored lemon yellow.
• Auscultation reveals a 2/6 systolic flow murmur over the left sternal border.
• A stiff, unsteady gait; hyperreflexia; loss of positional and vibratory sense in the lower limbs.
Relevant Lab Findings
• Blood chemistry:
- hemoglobin (Hgb) 10.5 ug/L (low);
- mean corpuscular volume (MCV) 120 fL (high);
- leukocyte count 3,400/mm3 (low);
- platelet count 78,000/mm3 (low);
B12 85 pg/mL (low);
- methylmalonic acid high;
- parietal cell autoantibodies high;
blood urea nitrogen (BUN) normal;
- creatinine normal
• Peripheral blood smear: megaloblastic anemia; neutrophils with hypersegmented nuclei
• Schilling test: positive
Diagnosis: Pernicious Anemia
• Pernicious Anemia.
Pernicious anemia is an autoimmune disease that is associated with a predisposition to other autoimmune disorders (particularly of the adrenal and thyroid glands).
Parietal cell autoantibodies develop, which causes a chronic fundal (type A) gastritis and pari
etal cell destruction. Parietal cells normally produce HCl and intrinsic factor (which is neces
sary for vitamin B12 absorption). The lack of intrinsic factor causes vitamin B12 deficiency,
which leads to megaloblastic anemia and subacute combined degeneration of the posterior
and lateral spinal tracts due to impairment of methylcobalamin-dependent methionine syn
thesis. Vitamin B12 deficiency may also be caused by surgical resection of the stomach or ileum,
Crohn disease, strict vegan diet, bacterial overgrowth, or Diphyllobothrium latum
Beriberi is a disease caused by thiamine deficiency often due to alcoholism. Dry
beriberi (first stage) is characterized by peripheral neuropathy. Wet beriberi (second stage)
is characterized by high-output heart failure. Wernicke-Korsakoff syndrome (final stage)
is characterized by confusion, ataxia, ophthalmoplegia, and confabulation.
. Clinical findings of diabetes include a diabetic peripheral neuropathy, gastro
paresis, and the inability to regulate heart rate.
• Folate Deficiency.
Folate deficiency may be caused by alcoholism, certain diets, pregnancy,
celiac sprue, giardiasis, phenytoin, oral contraceptives, and antifolate chemotherapeutic
agents. Clinical findings of folate deficiency include megaloblastic anemia but not suba
cute combined degeneration of the posterior and lateral spinal tracts.
• Lead Poisoning
. Clinical findings of lead poisoning include motor neuropathy leading to
wrist or foot drop; a microcytic, hypochromic anemia; basophilic stippling of RBCs; en
cephalopathy; Fanconi syndrome; and a lead line deposit in the gums.
Uremia is defined as elevated BUN and creatinine levels in the blood usually as a
result of renal failure. Clinical findings of uremia include anemia, peripheral neuropathy,
bleeding, heart failure, pericarditis, esophagitis, pruritus, and encephalopathy.