Micronutrient deficiencies — formative SAQs

SAQ 1 — The iron-deficient toddler (20 marks, ~15 minutes)

A two-year-old boy is referred with pallor, tiredness and irritability over three months. His mother reports that he eats little solid food, drinks around eight hundred millilitres of cow's milk a day, and has recently begun eating handfuls of garden soil. His weight has fallen from the fiftieth to the fifteenth centile. A full blood count shows a haemoglobin of eighty-two grams per litre with a mean cell volume of sixty-two femtolitres. [1]

Questions

1. Give the most likely diagnosis and the three features of the history and blood film that support it. (5 marks) [1]
2. Outline the confirmatory iron studies and explain why a C-reactive protein must accompany the ferritin. (5 marks) [1]
3. Outline the management, including the oral iron dose, the expected timeline of response and the dietary advice. (5 marks) [2]
4. Give the differential diagnosis of microcytic anaemia and the single feature that best separates iron deficiency from thalassaemia trait. (3 marks) [1]
5. Explain the rationale for universal iron screening at around twelve months. (2 marks) [1]

Model answer (must-hit)

1. The most likely diagnosis is iron-deficiency anaemia. The supporting features are the microcytic anaemia on the blood film with a low mean cell volume, the pallor and fallen growth centile, and the dietary history of excessive cow's milk intake with pica, the eating of soil, which is a classic clue. [1]
2. The confirmatory tests are a low serum ferritin, a low transferrin saturation, a raised transferrin and a low reticulocyte count. The C-reactive protein is required because ferritin is an acute-phase reactant that rises with inflammation and can mask iron deficiency, so a normal ferritin in a sick or inflamed child does not exclude it. [1]
3. The management is oral elemental iron at around three milligrams per kilogram per day, with dietary advice to limit cow's milk to around five hundred millilitres a day and introduce iron-rich solids. The reticulocyte count should rise within one to two weeks, the haemoglobin should normalise within two to three months, and the iron should be continued for about three months after the haemoglobin normalises to replete the stores. [2]
4. The differential of microcytic anaemia is iron deficiency, thalassaemia trait, anaemia of chronic disease, lead poisoning and sideroblastic anaemia. The feature that best separates iron deficiency from thalassaemia trait is the serum ferritin, which is low in iron deficiency and normal or raised in thalassaemia trait, alongside a normal or near-normal haemoglobin and a positive family history in thalassaemia. [1]
5. Universal iron screening at around twelve months is recommended because iron deficiency harms the developing brain, through dopamine and myelination, before the anaemia appears, so waiting for pallor is waiting too long. The neurodevelopmental argument, not the anaemia alone, is the case for screening. [1]

SAQ 2 — The breastfed infant of a vegan mother (20 marks, ~15 minutes)

An eight-month-old, exclusively breastfed infant of a strict vegan mother presents with a two-month history of increasing lethargy, poor feeding, floppiness, a fine tremor and loss of the ability to sit without support, which she had gained at seven months. On examination she is pale, hypotonic and apathetic. Her full blood count shows a haemoglobin of seventy-eight grams per litre with a mean cell volume of one hundred and five femtolitres. [7]

Questions

1. Give the most likely diagnosis and the features that support it. (5 marks) [7]
2. Outline the confirmatory investigations, including the role of methylmalonic acid. (5 marks) [8]
3. Explain the pathophysiology that links the macrocytic anaemia to the neurological injury. (4 marks) [7]
4. Outline the urgent management and explain why parenteral therapy is preferred. (4 marks) [8]
5. Outline the prevention for the mother and any future infant. (2 marks) [7]

Model answer (must-hit)

1. The most likely diagnosis is vitamin B12 deficiency in the exclusively breastfed infant of a vegan mother. The supporting features are the macrocytic anaemia on the blood film, the developmental regression with loss of sitting, the tremor and hypotonia, and the maternal vegan diet that depletes the breast milk of B12. The neurological signs can precede the anaemia, so the picture is fully consistent even before the film. [7]
2. The confirmatory tests are a low or borderline serum vitamin B12, a raised methylmalonic acid and a raised homocysteine, with a full blood count showing macrocytosis and hypersegmented neutrophils. The methylmalonic acid is raised when cellular B12 is deficient and helps confirm the diagnosis when the serum B12 is borderline, because it reflects functional intracellular depletion. The maternal serum B12 and dietary history complete the workup. [8]
3. Vitamin B12 is a cofactor for DNA synthesis, through the conversion of methylmalonyl-coenzyme A to succinyl-coenzyme A and the remethylation of homocysteine, so its deficiency blocks red-cell maturation and produces the large, fragile megaloblastic red cells of macrocytic anaemia. It is also needed for myelin maintenance, so its deficiency demyelinates the dorsal and lateral columns and the developing brain, producing the neurological injury. The two injuries share a single cause. [7]
4. The urgent management is parenteral hydroxocobalamin, daily for the first weeks then regular maintenance, started immediately the diagnosis is suspected because the neurological injury is severe and may not fully reverse. Parenteral therapy is preferred to bypass any absorptive defect and to deliver reliable replacement, and the mother is supplemented and counselled on a reliable B12 source. [8]
5. Prevention for the mother and any future infant is a reliable source of vitamin B12, through a supplement or B12-fortified foods, continued through pregnancy and lactation, with the infant given a B12 supplement from birth if exclusively breastfed by a vegan mother. [7]