Megaloblastic and macrocytic anaemia: Case

This infant has severe vitamin B12 deficiency acquired from the marginal stores of a strict vegan mother through exclusive breastfeeding. The macrocytic anaemia with oval macrocytes and hypersegmented neutrophils establishes the megaloblastic picture, the low serum B12 with both methylmalonic acid and homocysteine raised confirms B12 rather than folate deficiency, and the developmental regression with the tremor marks the neurological involvement that decides the urgency and the replacement schedule. [1][8]

Clinical findings and assessment

The key findings are the macrocytic anaemia with the hypersegmented neutrophils, the mild thrombocytopenia of the pancytopenia of impaired DNA synthesis, and the neurological signs of developmental regression and tremor. The raised lactate dehydrogenase with a normal haptoglobin reflects the ineffective erythropoiesis of the megaloblastic marrow, in which the red cell precursors die in the marrow and release their enzymes, rather than a haemolysis that would lower the haptoglobin. [1][5]

The history establishes the cause. The infant is exclusively breastfed, and the mother is a strict vegan, so the marginal maternal stores are the only source for the rapidly growing infant, and the supply is depleted within months. The neurological examination documents the lost head control, the coarse tremor, and the hypotonia, and the developmental screen records the milestones the infant has lost, because the severity and the duration of the deficit at presentation predict the completeness of the recovery. [9]

Diagnostic confirmation

The diagnosis is confirmed by the metabolites. Methylmalonic acid is raised only in B12 deficiency, through the methylmalonyl-CoA mutase reaction that B12 catalyses, and homocysteine is raised in both B12 and folate deficiency, through the shared methionine synthase step. Both metabolites raised therefore identifies B12 deficiency and excludes folate deficiency, and it resolves the diagnosis when the serum B12 is borderline, which it often is because the assay is confounded by pregnancy and liver disease. A bone marrow aspirate is not needed here, because the peripheral blood film and the metabolites are diagnostic, and the marrow is reserved for the atypical or pancytopenic case without a clear vitamin deficiency. [5][1]

Management

The management rests on parenteral hydroxocobalamin and two safety rules. For deficiency with neurological involvement, the British Society for Haematology schedule is hydroxocobalamin 1000 micrograms intramuscularly on alternate days for up to three weeks, or until no further improvement, followed by maintenance of 1000 micrograms every two to three months. Hydroxocobalamin is preferred over cyanocobalamin because it is retained longer, and the intramuscular route is reliable where the oral absorption is variable. [3]

The first safety rule is that folic acid is never given alone until B12 is excluded, which the metabolites have done here, so the folate can be given if the level is also low but only alongside the B12, because folate alone can precipitate or worsen subacute combined degeneration of the cord. The second safety rule is that the serum potassium is monitored and supplemented in the first days of replacement, because the resuming marrow takes up potassium and a severe hypokalaemia can develop. The severely anaemic child is transfused slowly if there is any sign of circulatory compromise, because the aim is to lift the haemoglobin only enough to relieve the strain on the heart while the vitamin replacement does the definitive work. [1][3]

Outcome and family counselling

The prognosis is excellent for the blood count, which corrects within weeks, and conditional for the nervous system, which recovers over months and incompletely if the deficit was severe and prolonged. The infant is therefore followed by a neurodevelopmental service for the re-acquisition of the lost milestones, and the family is prepared for a recovery that is measured in months rather than days. [9]

I would counsel the family honestly and warmly. I would explain that their infant has a deficiency of vitamin B12, that the vegan maternal diet left the milk short of the vitamin, and that the replacement will correct the blood count and improve the nervous system, though the recovery of the development will take time. I would teach the two safety rules, that the folic acid is never given alone and that the potassium is watched in the first days, and I would arrange the testing and the treatment of the mother and the dietary counselling of the family, with the breastfeeding continued alongside the replacement. I would reassure the family that the cause is reversible and that a team will follow the infant's development closely. [8][2]