A Specific Subtype of Sitosterolemia with Macrothrombocytopenia in a Chinese Family.

Background and Objective. Sitosterolemia is a rare autosomal recessive inherited disorder of lipoprotein metabolism characterized by xanthomas, premature coronary artery disease, arteriosclerosis and increased plasma levels of phytosterols, while hematological abnormalities such as large platelets have seldom been described. Recently, we found a Chinese family with sitosterolemia; three children suffered from sitosterolemia, who presented with obviously large platelets, some as large as erythrocytes. Their platelet volume distribution curves were displaced rightward. The patients’ bleeding time (11,12 and 15 min) was longer than normal range (4–8 min). The platelets could normally aggregate in response to collagen and ADP, but failed to agglutinate in the presence of 1.2-mg/ml ristocetin. Platelet membrane glycoproteins (GP)IIb/IIIa and GPIb were normal. Their parents are consanguineous. In this study, we characterized the clinical, biochemical and molecular genetic features of a Chinese family with sitosterolemia that mainly manifested hematological abnormalities.

Design and Methods. The clinical features of the affected patients in this family were analyzed. Their plasma sterol levels were measured by HPLC method. ABCG5 and ABCG8 genes sequencing searched for the mutation.

Results. The main clinical feature of the three affected patients was macrothrombocytopenia; they had increased plasma sitosterol, stigmasterol and cholestanol levels, but maintained normal cholesterol levels. Sequence analysis of ABCG5 and ABCG8 genes revealed a C to T transition at nucleotide 18802 resulting in a nonsense mutation in ABCG5 exon 1, Gln22X. The affected patients were homozygous whereas their parents and other two family members were heterozygous for this defect. Allele-specific restriction enzyme analysis using BfaIdid not detect this mutation in 70 healthy individual.

Interpretation and Conclusions. A few patients with sitosterolemia may present with obvious macrothrombocytopenia. It suggests that the blood cells could be a “target” in the toxic effect of phytosterols in plasma, the hematological abnormalities might represent a specific subtype of sitosterolemia. Therefore, it is necessary to propose that sitosterolemia should be considered in the differential diagnosis of macrothrombocytopenia. A novel nonsense mutation in ABCG5 was reported.