Victor Hoffbrand and Ralph Green

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Introduction, 60 Underlying basic science, 60

Biochemical basis of megaloblastic anaemia, 60 Cobalamin-folate relationship, 61 Clinical features, 63

General tissue effects of cobalamin and folate deficiencies, 63 Haematological findings, 65 Peripheral blood, 65 Bone marrow, 65 Chromosomes, 66 Ineffective haemopoiesis, 66 Cobalamin, 67

Dietary sources and requirements, 67 Absorption, 68 Enterohepatic circulation, 68 Transport, 69

Cobalamin analogues, 69 Causes of cobalamin deficiency, 69

Inadequate dietary intake, 69

Gastric causes of cobalamin malabsorption, 70

Intestinal causes of cobalamin malabsorption, 72 Abnormalities of cobalamin metabolism, 74 Diagnosis of cobalamin deficiency, 74

Deoxyuridine suppression test, 75 Measurement of the serum cobalamin, 75 Serum holotranscobalamin (HoloTCII; Holo TC), 75 Serum methylmalonate and homocysteine levels, 75

Tests for the cause of cobalamin deficiency, 76

Cobalamin absorption, 76

Folate, 76

Dietary folate, 76

Body stores and requirements, 77

Absorption, 77

Enterohepatic circulation, 77

Transport, 77

Biochemical functions, 77

Causes of folate deficiency, 78

Nutritional, 78

Malabsorption, 79

Excess utilization or loss, 79

Diagnosis of folate deficiency, 80

Serum folate, 80

Red cell folate, 80

Serum homocysteine , 80

General management of megaloblastic anaemia, 81 Treatment of cobalamin deficiency, 81 Treatment of folate deficiency, 81 Folinic acid (5-formyltetrahydrofolate), 81 Prophylactic folic acid, 81 Pregnancy, 82 Prematurity, 82

Haemolytic anaemia and dialysis, 82 Megaloblastic anaemia not due to cobalamin or folate deficiency or altered metabolism, 82 Other nutritional anaemias, 82 Protein deficiency, 82 Scurvy, 82

Other deficiencies, 82 Selected bibliography, 83

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