Stomatocytic haemolysis and macrothrombocytopenia (Mediterranean stomatocytosis/macrothrombocytopenia) is the haematological presentation of phytosterolaemia.
Phytosterolaemia (sitosterolaemia) is a recessively inherited metabolic condition in which the absorption of both cholesterol and plant-derived cholesterol-like molecules at the gut is unselective and unrestricted. In haematology, Mediterranean stomatocytosis or Mediterranean macrothrombocytopenia is a poorly understood haematological condition that combines stomatocytic haemolysis with the presence of very large platelets. Five pedigrees showing this haematology were identified. Gas chromatography mass spectrometry (GC-MS) showed that all of the patients with this highly specific haematology had grossly elevated levels of phytosterols in the blood, diagnostic of phytosterolaemia. All showed mutations in the ABCG5 and ABCG8 previously linked to phytosterolaemia. Three pedigrees showed five new mutations, while two pedigrees showed the common W361X mutation in ABCG8. We draw the following four conclusions: (i) that Mediterranean stomatocytosis/macrothrombocytopenia is caused by an excess of phytosterols in the blood; (ii) that phytosterolaemia, which does not respond to standard statin treatment, can be diagnosed via the distinctive haematology described here, even when the cholesterol is normal; (iii) that phytosterolaemia should be considered in the differential diagnosis of all patients with large platelets; and (iv) that the platelet size should be noted in patients with hypercholesterolaemia.
Rees
David C
DC
Sheffield Children's Hospital, Royal Hallamshire Hospital, Sheffield, UK.
Iolascon
Achille
A
Carella
Massimo
M
O'marcaigh
Aengus S
AS
Kendra
James R
JR
Jowitt
Simon N
SN
Wales
J K
JK
Vora
Ajay
A
Makris
M
M
Manning
Nigel
N
Nicolaou
Anna
A
Fisher
Julie
J
Mann
Anuska
A
Machin
Samuel J
SJ
Clayton
Peter T
PT
Gasparini
Paolo
P
Stewart
Gordon W
GW
D000071018:ATP Binding Cassette Transporter, Subfamily G, Member 5; D000071019:ATP Binding Cassette Transporter, Subfamily G, Member 8; D018528:ATP-Binding Cassette Transporters / Q000235:genetics; D000293:Adolescent; D000328:Adult; D001792:Blood Platelets / Q000502:physiology / Q000648:ultrastructure; D002648:Child; D004910:Erythrocyte Membrane / Q000737:chemistry; D004913:Erythrocytes, Abnormal / Q000473:pathology*; D005260:Female; D006461:Hemolysis; D006801:Humans; D008074:Lipoproteins / Q000235:genetics; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D009154:Mutation; D010375:Pedigree; D010840:Phytosterols / Q000097:blood*; D043202:Steroid Metabolism, Inborn Errors / Q000097:blood / Q000150:complications* / Q000235:genetics; D013921:Thrombocytopenia / Q000097:blood / Q000209:etiology* / Q000235:genetics
C416945:ABCG5 protein, human; C416946:ABCG8 protein, human; D000071018:ATP Binding Cassette Transporter, Subfamily G, Member 5; D000071019:ATP Binding Cassette Transporter, Subfamily G, Member 8; D018528:ATP-Binding Cassette Transporters; D008074:Lipoproteins; D010840:Phytosterols