Differentials
Vitamin B12 (cobalamin) deficiency
SIGNS / SYMPTOMS
May be associated with neurological and neuropsychiatric manifestations, specifically: decreased vibration sense, peripheral neuropathy, gait abnormalities, dementia, depression, and visual impairment.
Clinical and haematological response to treatment confirms diagnosis.
INVESTIGATIONS
Serum vitamin B12 levels are low.
Both homocysteine and methylmalonic acid are elevated.
Thiamine-responsive megaloblastic anaemia
SIGNS / SYMPTOMS
Diabetes mellitus and sensorineural deafness are present, in addition to megaloblastic anaemia.
Megaloblastic anaemia and diabetes mellitus respond partially to thiamine therapy.
INVESTIGATIONS
Ringed sideroblasts are seen in the bone marrow.
Serum folate level is normal.
Hereditary orotic aciduria
SIGNS / SYMPTOMS
Growth retardation, neurological abnormalities, and obstructive uropathy are associated with hypochromic megaloblastic anaemia, with or without congenital malformations and immune deficiency.
Replacement of uridine corrects anaemia, reduces orotic crystalluria, and improves other sequelae.
INVESTIGATIONS
Orotic acid crystalluria is present.
Serum folate level is normal.
Alcoholic liver disease
SIGNS / SYMPTOMS
Nutritional deficiencies and macrocytic anaemia may be the presenting features. History reveals alcohol misuse.
INVESTIGATIONS
Elevated liver enzymes.
Liver biopsy shows fatty liver, inflammation, and/or cirrhosis.
Hypothyroidism
SIGNS / SYMPTOMS
Constipation, weight gain, cold intolerance, hoarse voice, bradycardia, dry/rough skin, delayed tendon reflexes.
INVESTIGATIONS
Elevated thyroid-stimulating hormone, low T4, and low T3.
Serum folate level is normal. Homocysteine levels are often elevated.[60]
Myelodysplastic syndrome
SIGNS / SYMPTOMS
Gradual-onset fatigue often present, and 20% of patients have splenomegaly.
May be associated with prior chemotherapy or radiation exposure.
INVESTIGATIONS
Macrocytic anaemia may be associated with neutropenia and thrombocytopenia.
Peripheral smear findings include dimorphic anaemia; large, hypogranular platelets; hypogranulated, hyposegmented neutrophils with Dohle bodies; and circulating myeloblasts.
Bone marrow shows dyserythropoiesis; hypogranulated, hyposegmented granulocytic precursors; increased myeloblasts; and megakaryocytes showing fewer or disorganised nuclei. Ringed sideroblasts are seen in the bone marrow in certain sub-types of myelodysplastic syndrome.
Cytogenetic analysis and fluorescence in-situ hybridisation can identify specific chromosomal abnormalities.
Mutations in specific genes are associated with myelodysplasia.
Aplastic anaemia
SIGNS / SYMPTOMS
History of prior viral illness, chemical exposure, or drug use may be present.
Bleeding, lassitude, and symptoms of infection are usually present. Ecchymosis and signs of infection may be present, in addition to pallor.
INVESTIGATIONS
Macrocytic anaemia, neutropenia, thrombocytopenia, and reticulocytopenia are present. Absence of glycosylphosphatidylinositol-anchored proteins, when associated with paroxysmal nocturnal haemoglobinuria.
Bone marrow aspirate and biopsy show decreased cellularity and paucity of all three lineage precursors.
Pure red blood cell aplasia
SIGNS / SYMPTOMS
If in infancy, family history may be present.
May be associated with abnormal phenotype, and with signs and symptoms related to cardiovascular and renal anomalies.
INVESTIGATIONS
Macrocytic anaemia and reticulocytopenia are the hallmarks.
Elevated erythrocyte adenosine deaminase is present in 70% to 80% of patients. Ribosomal protein genes and GATA1 mutations in Diamond-Blackfan anaemia.
Bone marrow examination shows isolated red blood cell hypoplasia or aplasia. Other cell lines are generally uninvolved.
Drug-induced macrocytosis
SIGNS / SYMPTOMS
Associated with intake of certain drugs, such as DNA synthesis-inhibiting drugs, immunosuppressive drugs, anticonvulsants, and antiviral medications.
INVESTIGATIONS
Usually a clinical diagnosis.
Serum folate level is normal.
Diphyllobothriasis
SIGNS / SYMPTOMS
Presents with abdominal discomfort, diarrhoea, vomiting, weakness, weight loss, and occasionally acute abdominal pain due to intestinal obstruction, cholangitis, or cholecystitis. Additional features are megaloblastic anaemia and neurological abnormalities secondary to vitamin B12 (cobalamin) deficiency.
INVESTIGATIONS
Stool examination reveals characteristic eggs of the fish tapeworm Diphyllobothrium latum.
Serum vitamin B12 levels are low.
Serum folate is normal.
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