Haematological presentation of sitosterolaemia

Sitosterolaemia is an autosomal recessive disorder in which the intestinal absorption of sterol molecules is unregulated, leading to elevated cholesterol. Recognition avoids unnecessary investigation. A low plant sterol diet reduces symptoms, anaemia and cardiovascular risk. We identified a patient in an isolated Scottish island community by recognising the key haematological finding of macrothrombocytopenia and haemolytic anaemia (without raised cholesterol). Serum gas chromatography demonstrated significantly raised sitosterol levels. Sequencing revealed homozygosity for the most common ABCG8 pathogenic variant, c.1083G>A, p.Trp361Ter (W361X), confirming the diagnosis.Homozygosity for a rare variant suggested its enrichment in Scottish island populations. Interrogation of data from the Viking Genes Project cohort confirmed a significant increase in variant heterozygosity in those with four Scottish island grandparents compared to the general UK population. We propose that sitosterolaemia is under-recognised. It should be considered in patients with macrothrombocytopenia and haemolytic anaemia, especially in those of Scottish island ancestry.