R Khurana, P Kanvinde, M Desai, N Shah, A Swami, M Bodhanwala, S
Mudaliar
Sitosterolemia is a rare autosomal recessive disease of plant sterol
metabolism. Bhattacharyya and Connor first described this disease in
1974 (1). To date, there are only about 100 known cases worldwide (2).
We describe two patients diagnosed with Sitosterolemia at our centre.
Patient A is a 12 year old male, presented with complaints of short
stature, abdominal distension & gradually progressive paleness since 2
months. He had pallor, hemolytic facies and both weight (25kg) & height
(130cm) were less than 3rd centile and had
spleno-hepatomegaly.
His investigations (table1) were suggestive of a chronic hemolytic
anemia. Since the child did not have spherocytes on peripheral smear &
had giant platelets, diagnosis of hereditary spherocytosis seemed
unconvincing. So genetic work up by next generation sequencing was done
which revealed mutation in ABCG8 gene, suggestive of Sitosterolemia. On
review, his peripheral smear showed some stomatocytes (figure1).
Patient B is a 12 year old child who was referred to us for splenectomy.
Child had splenomegaly bicytopenia, diagnosed during work up for a short
febrile illness. There were stomatocytes in his smear too & sterol
levels were borderline high, hence genetic studies were sent, which
revealed compound heterozygous variants in the ABCG5 gene, suggestive of
Sitosterolemia type 2.
Both the patients are under regular follow up for monitoring diet,
counts & changes of early atherosclerosis. If dietary changes are not
adequate, we will consider ezitimibe for them.
Discussion
Patients with Sitosterolemia can have a variety of presentations like
short stature, chronic abdominal discomfort, splenomegaly etc indicating
a chronic hemolytic disease. Some may present with tendinous and
cutaneous xanthomas, arthritis, and arthralgias. They have a strong
propensity towards premature coronary atherosclerosis (3).
Laboratory features are suggestive of chronic hemolysis with presence of
stomatocytic red cells and macrothrombocytopenia on blood films. Eosin
5’ maleimide test by flow cytometry (EMA) is usually abnormal. Plasma
levels of plant sterols (sitosterol, cholestanol, and stigmasterol)
measured by GC-MS (gas chromatography-mass spectrometry) are elevated.
The identified homozygous or compound heterozygous mutations in ABCG5
and ABCG8 genes further confirm the diagnosis.
Treatment predominantly involves dietary changes & pharmacological
adjuncts. All sources of vegetable fats like vegetable oils, nuts,
seeds, olives, avocados etc. should be eliminated. Food derived from
animal sources with cholesterol as the dominant source should be allowed
(4). Bile acid resins like cholestyramine may be useful, statins have no
role (5). Ezetimibe was US FDA approved in 2002 for use in patients with
sitosterolemia. Ezetimibe alone or in combination with cholestyramine
effectively reduces plant sterol levels by around 50%(6). Some patients
may require surgical interventions like ileal bypass to effectively
reduce sterol levels.
We feel that this condition is under reported as many may remain
misdiagnosed as hereditary spherocytosis or hyperlipidemias. Measures as
simple as dietary modification can control this condition & prevent a
splenectomy(which will be detrimental in patients with Sitosterolemia).
Hence, stomatocytes should be actively searched for in patients with
large platelets and unexplained mild hemolysis. Consider early NGS to
determine diagnosis.
References
- Bhattacharyya AK, Connor WE. Beta-sitosterolemia and xanthomatosis. A
newly described lipid storage disease in two sisters. J Clin Invest.
1974;53(4):1033-1043.
- Kidambi S, Patel SB. Sitosterolaemia: pathophysiology, clinical
presentation and laboratory diagnosis. J Clin Pathol. 2008;
61(5):588-594.
- Merkens LS, Myrie SB, Steiner RD, Mymin D. Sitosterolemia.
GeneReviews [Internet] Seattle (WA): University of Washington;
2016. [updated 2013 Apr 4].
- EscolaGil JC, Quesada H, Julve J, MartinCampos JM, Cedo L,
BlancoVaca F. Sitosterolemia: diagnosis, investigation, and
management. Curr Atheroscler Rep 2014;16:424.
- Parsons HG, Jamal R, Baylis B, Dias VC, Roncari D. A marked and
sustained reduction in LDL sterols by diet and cholestyramine in
betasitosterolemia. Clin Invest Med 1995;18:389400.
- Lutjohann D, von Bergmann K, Sirah W, Macdonell G, JohnsonLevonas AO,
Shah A, et al. Longterm efficacy and safety of ezetimibe 10 mg in
patients with homozygous sitosterolemia: a 2year, openlabel
extension study. Int J Clin Pract 2008;62:1499510.