Sideroblastic anaemia

This is the fourth and final article in a series about anaemia. First article: anaemia. Previous article: Anaemia of chronic disease.

Sideroblastic anaemia (SA) is like haemochromatosis as there is too much iron. Due to an absence of protoporphyrin iron transport is inhibited. SA’s include hereditary and acquired conditions; these can be due to alcohol, toxins, congenital defects, malignancies, or mutations. This haem synthesizing defect can be caused by the X-linked chromosome or the lead poisoning induced mutations, these are main mutations that interrupt the 8 enzymatic cascades in the biosynthesis of protoporphyrin, thus leading to defective haemoglobin (Hg) moreover, iron accumulation in the mitochondria. X-linked protoporphyria is due to a germline mutation in the gene that produces δ-aminolaevulinic acid (δ-ala) synthase, this interrupts the first step of haem synthesis, figure 1. Lead poisoning can interrupt 2 stages of haem synthesis δ-ala dehydratase (-δ-ala dehydratase porphyria) and ferrochelatase (erythropoietic protoporphyria). The first step devastates the production of haem, due to the chromosomal abnormality that stops the production of δ-ala dehydratase, is X-linked porphyria. The second step and the final step are associated with lead poisoning, this is more common in children. Ferrochelatase is a catalyst for the incorporation of iron to haem in the final stage of haemoglobin synthesis, this causes ferrochelatase erythrocytic protoporphyrin (FECH EPP).

SA clinical presentation

Common features of SA are general to microcytic anaemias such as teardrop and hypochromic cells, dimorphism is common, pappenheimer bodies and mitochondrial iron clusters which are found in bone marrow smears, where iron accumulates around 2/3 of the nucleus of erythroblasts. Without knowing the aetiology of anaemia standard FBCs and iron studies would be run to initially diagnosis the anaemia, with SA the iron cannot be transported so transferrin will be reduced, alongside mean cell volume (MCV), haemoglobin and haematocrit (HCT). There will also be an increase in ferratin, % saturation and serum Fe. Microcytic anaemia presents in 20-60% of patients with FECH-EPP. morphology will present as microcytic and hypochromic with the possible presentation of Pappenheimer bodies, ringed sideroblasts, dimorphism and basophilic stippling may be present in bloods of children suspected in lead >5 µg/dL. Lead poisoning can be misdiagnosed as porphyrin as lead is shed from the body slowly, this allows approximately 80% of the lead to be absorbed. Although lead exits the blood rather quickly once it’s in the bone it can have a half-life of 30 years.

Written by Lauren Kelly