MCID: STS003
MIFTS: 56

Sitosterolemia malady

Categories: Genetic diseases, Rare diseases, Metabolic diseases, Endocrine diseases

Aliases & Classifications for Sitosterolemia

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Sources:
49OMIM, 11diseasecard, 21GeneReviews, 45NIH Rare Diseases, 22GeneTests, 23Genetics Home Reference, 47Novoseek, 51Orphanet, 67UniProtKB/Swiss-Prot, 24GTR, 65UMLS, 28ICD10 via Orphanet, 37MESH via Orphanet, 66UMLS via Orphanet, 34MedGen, 61The Human Phenotype Ontology
See all MalaCards sources

Aliases & Descriptions for Sitosterolemia:

Name: Sitosterolemia 49 11 21 45 22 23 47 51 67 24 65
Phytosterolemia 21 45 22 23 51 67
Beta-Sitosterolemia 21 22 23
Plant Sterol Storage Disease 45 23
Phytosterolaemia 22 23
Sitosterolaemia 22 23
Retention of Dietary Cholesterol and Abnormal Retention of Non-Cholesterol Sterols in the Body 45
 
Sitosterolemia with Xanthomatosis 65
Xanthomatosis with Sisterolemia 51
Shellfish Sterolemia 67
Phytosterolæmia 21
Sitosterolæmia 21
Stsl 67

Characteristics:

Orphanet epidemiological data:

51
sitosterolemia:
Inheritance: Autosomal recessive; Prevalence: <1/1000000 (Worldwide); Age of onset: All ages

HPO:

61
sitosterolemia:
Inheritance: autosomal recessive inheritance


Classifications:



External Ids:

OMIM49 210250
Orphanet51 2882
ICD10 via Orphanet28 E78.0
MESH via Orphanet37 C537345
UMLS via Orphanet66 C0342907
UMLS65 C0342907, C0268202

Summaries for Sitosterolemia

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NIH Rare Diseases:45 Sitosterolemia is a rare inherited condition in which plant sterols accumulate in the blood and tissues. plant sterols, including sitosterol, stigmasterol, and campesterol, are fatty substances found in vegetable oils and nuts. individuals with sitosterolemia have extremely high levels of sitosterol (30 to 100 times higher than normal), along with mildly to moderately elevated levels of cholesterol in their blood. these plant sterols and cholesterol build up in the arteries, leading to premature thickening of the artery walls and early heart disease. affected individuals may also develop small yellowish growths called xanthomas on or under the skin and in the tendons. sitosterolemia is caused by mutations in the abcg5 or abcg8 gene. the condition is inherited in an autosomal recessive pattern. treatment involves restricting foods that are high in plant and shellfish sterols, and taking medications that decrease the concentration of these products in the blood. last updated: 4/12/2016

MalaCards based summary: Sitosterolemia, also known as phytosterolemia, is related to cerebrotendinous xanthomatosis and xanthomatosis, and has symptoms including hyperapobetalipoproteinemia, coronary atherosclerosis and chronic hemolytic anemia. An important gene associated with Sitosterolemia is ABCG8 (ATP Binding Cassette Subfamily G Member 8), and among its related pathways are Vitamin A and carotenoid metabolism and Bisphosphonate Pathway, Pharmacodynamics. Affiliated tissues include heart, liver and skin, and related mouse phenotypes are liver/biliary system and growth/size/body region.

UniProtKB/Swiss-Prot:67 Sitosterolemia: Rare autosomal recessive disorder characterized by increased intestinal absorption of all sterols including cholesterol, plant and shellfish sterols, and decreased biliary excretion of dietary sterols into bile. Sitosterolemia patients have hypercholesterolemia, very high levels of plant sterols in the plasma, and frequently develop tendon and tuberous xanthomas, accelerated atherosclerosis and premature coronary artery disease.

Genetics Home Reference:23 Sitosterolemia is a condition in which fatty substances (lipids) from vegetable oils, nuts, and other plant-based foods accumulate in the blood and tissues. These lipids are called plant sterols (or phytosterols). Sitosterol is one of several plant sterols that accumulate in this disorder, with a blood level 30 to 100 times greater than normal. Cholesterol, a similar fatty substance found in animal products, is mildly to moderately elevated in many people with sitosterolemia. Cholesterol levels are particularly high in some affected children.

OMIM:49 Sitosterolemia, also known as phytosterolemia, is an autosomal recessive metabolic condition characterized by... (210250) more...

Wikipedia:68 Sitosterolemia (also known as \"Phytosterolemia\") is a rare autosomal recessively inherited lipid... more...

GeneReviews summary for NBK131810

Related Diseases for Sitosterolemia

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Graphical network of the top 20 diseases related to Sitosterolemia:



Diseases related to sitosterolemia

Symptoms for Sitosterolemia

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Symptoms by clinical synopsis from OMIM:

210250

Clinical features from OMIM:

210250

HPO human phenotypes related to Sitosterolemia:

(show all 16)
id Description Frequency HPO Source Accession
1 hyperapobetalipoproteinemia HP:0008158
2 coronary atherosclerosis HP:0004929
3 chronic hemolytic anemia HP:0004870
4 episodic hemolytic anemia HP:0004802
5 stomatocytosis HP:0004446
6 impaired platelet aggregation HP:0003540
7 hypercholesterolemia HP:0003124
8 arthralgia HP:0002829
9 abdominal pain HP:0002027
10 reticulocytosis HP:0001923
11 giant platelets HP:0001902
12 abnormal bleeding HP:0001892
13 splenomegaly HP:0001744
14 abnormality of the integument HP:0001574
15 abnormality of the liver HP:0001392
16 arthritis HP:0001369

UMLS symptoms related to Sitosterolemia:


abdominal pain

Drugs & Therapeutics for Sitosterolemia

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Drugs for Sitosterolemia (from DrugBank, HMDB, Dgidb, PharmGKB, IUPHAR, NovoSeek, BitterDB):

(show all 10)
idNameStatusPhaseClinical TrialsCas NumberPubChem Id
1
EzetimibeapprovedPhase 3, Phase 2266163222-33-1150311
Synonyms:
(-)-Sch 58235
(1-(4-fluorophenyl)-(3R)-(3-(4-fluorophenyl)-(3S)-hydroxypropyl)-(4S)-(4-hydroxyphenyl)-2-azetidinone)
(3R,4S)-1-(4-fluorophenyl)-3-[(3S)-3-(4-fluorophenyl)-3-hydroxypropyl]-4-(4-hydroxyphenyl)azetidin-2-one
(3R,4S)-1-(p-Fluorophenyl)-3-((3S)-3-(p-fluorophenyl)-3-hydroxypropyl)-4-(p-hydroxyphenyl)-2-azetidinone
1-(4-fluorophenyl)-3(R)-[3-(4-fluorophenyl)-3(S)-(4-hydroxyphenyl)-2-azetidione
1-(4-fluorophenyl)-3(R)-[3-(4-fluorophenyl)-3(S)-hydroxypropyl]-4(S)-(4-hydroxyphenyl)-2-azetidinone
163222-33-1
AC-1057
AC1L442L
C108606
CHEBI:49040
CHEMBL1138
CID150311
CPD000466334
D01966
DB00973
Essex brand of ezetimibe
Ezedoc
Ezetimiba
Ezetimibe
Ezetimibe (JAN/USAN/INN)
Ezetimibe [USAN:INN]
Ezetimibum
 
Ezetrol
HMS2051K16
LS-181801
MK-0653
MLS000759443
MLS001424125
MSD brand of ezetimibe
Merck brand of ezetimibe
MolPort-005-938-627
S1655_Selleck
SAM001246623
SCH-58235
SCH58235
SMR000466334
STK640490
STOCK6S-73750
Sch 58235
Schering-Plough brand of ezetimibe
UNII-EOR26LQQ24
ZINC03810860
Zetia
Zetia (TN)
Zetia , Ezetrol, Ezetimibe
Zient
ezetimib
2Anticholesteremic AgentsPhase 3, Phase 21732
3Gamma-sitosterolPhase 3, Phase 25
4Hypolipidemic AgentsPhase 3, Phase 22228
5AntimetabolitesPhase 3, Phase 29454
6PhytosterolNutraceuticalPhase 193
7Insulin, Globin Zinc4278
8insulin4278
9Contraceptives, Oral3734
10Colesevelam Hydrochloride44

Interventional clinical trials:

(show all 13)
idNameStatusNCT IDPhase
1Higher-Dose Ezetimibe to Treat Homozygous SitosterolemiaCompletedNCT00099996Phase 3
2An Investigational Drug Study to Lower Non-Cholesterol Sterol Levels Associated With Sitosterolemia (0653-062)(COMPLETED)CompletedNCT00092898Phase 3
3Sitosterolemia Extension Study (0653-003)(COMPLETED)CompletedNCT00092807Phase 3
4Sitosterolemia Extension Study (0653-004)(COMPLETED)CompletedNCT00092820Phase 3
5Investigational Drug in Patients With Hypercholesterolemia or in Patients With Sitosterolemia (0653-026)(COMPLETED)TerminatedNCT00092833Phase 3
6SCH-58235 (Ezetimibe) to Treat Homozygous SitosterolemiaCompletedNCT00045812Phase 2
7Cholesterol Metabolism in Heterozygous PhytosterolemiaCompletedNCT01102647Phase 1
8Genetic Study of SitosterolemiaCompletedNCT00004481
9The Effect of Dietary Sitosterol on Blood Sugar and CholesterolCompletedNCT00531128
10A 52-week Post-marketing, Observational Study to Confirm the Safety and Efficacy of Zetia Alone or in Combination With Other Lipid-lowering Drugs in Japanese Subjects With Hypercholesterolemia (Study P05245)CompletedNCT00705211
11A 12-week Post-marketing, Observational Study to Confirm the Safety and Efficacy of Zetia Alone or in Combination With Other Lipid-lowering Drugs in Japanese Subjects With Hypercholesterolemia (Study P05244)CompletedNCT00704444
12Sitosterolemia MetabolismActive, not recruitingNCT01584206
13Effects of ColesevelamNot yet recruitingNCT01948648

Search NIH Clinical Center for Sitosterolemia

Genetic Tests for Sitosterolemia

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Genetic tests related to Sitosterolemia:

id Genetic test Affiliating Genes
1 Sitosterolemia22 ABCG8

Anatomical Context for Sitosterolemia

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MalaCards organs/tissues related to Sitosterolemia:

33
Heart, Liver, Skin, Testes, Prostate, Thyroid, Endothelial

Animal Models for Sitosterolemia or affiliated genes

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MGI Mouse Phenotypes related to Sitosterolemia:

38
idDescriptionMGI Source AccessionScoreTop Affiliating Genes
1MP:00053707.1ABCG1, ABCG5, ABCG8, APOB, CYP27A1, CYP7A1
2MP:00053787.1ABCG1, ABCG5, APOB, CYP7A1, FDFT1, HMGCR
3MP:00053766.6ABCG1, ABCG5, ABCG8, APOB, CYP27A1, CYP7A1

Publications for Sitosterolemia

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Articles related to Sitosterolemia:

(show top 50)    (show all 82)
idTitleAuthorsYear
1
Sitosterolemia: a review and update of pathophysiology, clinical spectrum, diagnosis, and management. (27104173)
2016
2
Two novel mutations in the ABCG5 gene, c.144 -1G&gt;A and c.1523 delC, in a Mexican family with sitosterolemia. (26892138)
2016
3
Hepatic or intestinal ABCG5 and ABCG8 are sufficient to block the development of sitosterolemia. (25527605)
2015
4
Sitosterolemia presenting with severe hypercholesterolemia and intertriginous xanthomas in a breastfed infant: case report and brief review. (24423340)
2014
5
Ezetimibe treatment should be considered for patients with sitosterolemia. (24839218)
2014
6
Platelet hyperreactivity explains the bleeding abnormality and macrothrombocytopenia in a murine model of sitosterolemia. (23926302)
2013
7
Specific macrothrombocytopenia/hemolytic anemia associated with sitosterolemia. (24166850)
2013
8
Current therapy for patients with sitosterolemia--effect of ezetimibe on plant sterol metabolism. (20543520)
2010
9
Genetic inactivation of NPC1L1 protects against sitosterolemia in mice lacking ABCG5/ABCG8. (18796403)
2009
10
Plant sterols cause macrothrombocytopenia in a mouse model of sitosterolemia. (18156627)
2008
11
Long-term efficacy and safety of ezetimibe 10 mg in patients with homozygous sitosterolemia: a 2-year, open-label extension study. (18822021)
2008
12
Similar serum plant sterol responses of human subjects heterozygous for a mutation causing sitosterolemia and controls to diets enriched in plant sterols or stanols. (17228349)
2007
13
Intestinal cholesterol absorption inhibitor ezetimibe added to cholestyramine for sitosterolemia and xanthomatosis. (16697747)
2006
14
Clinical and molecular genetic analysis of a family with sitosterolemia and co-existing erythrocyte and platelet abnormalities. (17018391)
2006
15
A detailed Hapmap of the Sitosterolemia locus spanning 69 kb; differences between Caucasians and African-Americans. (16507104)
2006
16
Dietary sitostanol and campestanol: accumulation in the blood of humans with sitosterolemia and xanthomatosis and in rat tissues. (16331855)
2005
17
A mouse model of sitosterolemia: absence of Abcg8/sterolin-2 results in failure to secrete biliary cholesterol. (15040800)
2004
18
Sitosterolemia in ABC-transporter G5-deficient mice is aggravated on activation of the liver-X receptor. (14699507)
2004
19
Ezetimibe effectively reduces plasma plant sterols in patients with sitosterolemia. (14769702)
2004
20
A 19-year-old man with myocardial infarction and sitosterolemia. (12879952)
2003
21
Novel donor splice site mutation of ABCG5 gene in sitosterolemia. (11855938)
2002
22
Mutations in ATP-cassette binding proteins G5 (ABCG5) and G8 (ABCG8) causing sitosterolemia. (11668628)
2001
23
Japanese sisters associated with pseudohomozygous familial hypercholesterolemia and sitosterolemia. (11425042)
2000
24
Sitosterolemia: exclusion of genes involved in reduced cholesterol biosynthesis. (9610773)
1998
25
Competitive inhibition of hepatic sterol 27-hydroxylase by sitosterol: decreased activity in sitosterolemia. (9460081)
1998
26
Down-regulation of cholesterol biosynthesis in sitosterolemia: diminished activities of acetoacetyl-CoA thiolase, 3-hydroxy-3-methylglutaryl-CoA synthase, reductase, squalene synthase, and 7-dehydrocholesterol delta7-reductase in liver and mononuclear leukocytes. (9469584)
1998
27
Mapping a gene involved in regulating dietary cholesterol absorption. The sitosterolemia locus is found at chromosome 2p21. (9727073)
1998
28
Sitosterolemia. (9090303)
1997
29
beta-Sitosterolemia with generalized eruptive xanthomatosis. (9152615)
1997
30
Coronary bypass grafts in a young girl with sitosterolemia. (8781841)
1996
31
A marked and sustained reduction in LDL sterols by diet and cholestyramine in beta-sitosterolemia. (8529322)
1995
32
Deficient ileal 3-hydroxy-3-methylglutaryl coenzyme A reductase activity in sitosterolemia: sitosterol is not a feedback inhibitor of intestinal cholesterol biosynthesis. (8028508)
1994
33
Biochemical studies of inherited diseases related to abnormal cholesterol metabolism. II: Absence of unusual C28 and C29 bile acid homologs in bile and urine of sitosterolemia. (7896564)
1994
34
Inverse relationship between plasma cholestanol concentrations and bile acid synthesis in sitosterolemia. (7852865)
1994
35
Sitosterolemia. (1431587)
1992
36
Regulation of cholesterol biosynthesis in sitosterolemia: effects of lovastatin, cholestyramine, and dietary sterol restriction. (1816322)
1991
37
Decreased cholesterol biosynthesis in sitosterolemia with xanthomatosis: diminished mononuclear leukocyte 3-hydroxy-3-methylglutaryl coenzyme A reductase activity and enzyme protein associated with increased low-density lipoprotein receptor function. (2325562)
1990
38
A molecular defect in hepatic cholesterol biosynthesis in sitosterolemia with xanthomatosis. (2394840)
1990
39
Increased plasma plant sterol levels in heterozygotes with sitosterolemia and xanthomatosis. (2380636)
1990
40
Increased sitosterol absorption, decreased removal, and expanded body pools compensate for reduced cholesterol synthesis in sitosterolemia with xanthomatosis. (2600539)
1989
41
The effect of abnormal plasma and cellular sterol content and composition on low density lipoprotein uptake and degradation by monocytes and lymphocytes in sitosterolemia with xanthomatosis. (3357417)
1988
42
Competitive inhibition of bile acid synthesis by endogenous cholestanol and sitosterol in sitosterolemia with xanthomatosis. Effect on cholesterol 7 alpha-hydroxylase. (3143743)
1988
43
Abnormal metabolism of shellfish sterols in a patient with sitosterolemia and xanthomatosis. (3711338)
1986
44
Lethal atherosclerosis associated with abnormal plasma and tissue sterol composition in sitosterolemia with xanthomatosis. (4067433)
1985
45
Synthesis and structure of 26 (or 27)-nor-5 beta-cholestane-3 alpha,7 alpha,12 alpha,24S,25 xi-pentol isolated from the urine and feces of a patient with sitosterolemia and xanthomatosis. (2985722)
1985
46
Identification of 5 alpha-stanols in patients with sitosterolemia and xanthomatosis: stereochemistry of the protonolysis of steroidal organoboranes. (6297129)
1982
47
A unique patient with coexisting cerebrotendinous xanthomatosis and beta-sitosterolemia. (7258222)
1981
48
Beta-sitosterolemia and xanthomatosis. (1246333)
1976
49
Beta-Sitosterolemia and xanthomatosis. (781555)
1976
50
Beta-sitosterolemia and xanthomatosis. A newly described lipid storage disease in two sisters. (4360855)
1974

Variations for Sitosterolemia

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UniProtKB/Swiss-Prot genetic disease variations for Sitosterolemia:

67 (show all 16)
id Symbol AA change Variation ID SNP ID
1ABCG5p.Glu146GlnVAR_012244
2ABCG5p.Arg389HisVAR_012245
3ABCG5p.Arg419HisVAR_012246
4ABCG5p.Arg419ProVAR_012247
5ABCG5p.Arg550SerVAR_012248
6ABCG5p.Asn437LysVAR_020781
7ABCG8p.Arg184HisVAR_012252
8ABCG8p.Pro231ThrVAR_012253
9ABCG8p.Arg263GlnVAR_012256rs137852990
10ABCG8p.Arg405HisVAR_012258
11ABCG8p.Leu501ProVAR_012259
12ABCG8p.Arg543SerVAR_012260rs201690654
13ABCG8p.Leu572ProVAR_012262
14ABCG8p.Gly574GluVAR_012263
15ABCG8p.Gly574ArgVAR_012264
16ABCG8p.Leu596ArgVAR_012266

Clinvar genetic disease variations for Sitosterolemia:

5 (show all 18)
id Gene Variation Type Significance SNP ID Assembly Location
1NM_022436.2(ABCG5): c.978delA (p.Glu326Aspfs)deletionLikely pathogenicrs869025350GRCh38Chr 2, 43824359: 43824359
2NM_022436.2(ABCG5): c.46C> T (p.Gln16Ter)single nucleotide variantPathogenicrs387906912GRCh37Chr 2, 44065773: 44065773
3NM_022436.2(ABCG5): c.1336C> T (p.Arg446Ter)single nucleotide variantPathogenicrs199689137GRCh37Chr 2, 44050063: 44050063
4ABCG8NM_022437.2(ABCG8): c.320C> G (p.Ser107Ter)single nucleotide variantPathogenicrs137854891GRCh37Chr 2, 44073448: 44073448
5ABCG8NM_022437.2(ABCG8): c.1083G> A (p.Trp361Ter)single nucleotide variantPathogenicrs137852987GRCh37Chr 2, 44099233: 44099233
6ABCG8NM_022437.2(ABCG8): c.1720G> A (p.Gly574Arg)single nucleotide variantPathogenicrs137852988GRCh37Chr 2, 44102516: 44102516
7ABCG8NM_022437.2(ABCG8): c.1974C> G (p.Tyr658Ter)single nucleotide variantPathogenicrs137852989GRCh37Chr 2, 44105004: 44105004
8ABCG8NM_022437.2(ABCG8): c.788G> A (p.Arg263Gln)single nucleotide variantPathogenicrs137852990GRCh37Chr 2, 44079831: 44079831
9ABCG8NM_022437.2(ABCG8): c.547delC (p.Gln183Serfs)deletionPathogenicrs387906323GRCh37Chr 2, 44078947: 44078947
10ABCG8NM_022437.2(ABCG8): c.1234C> T (p.Arg412Ter)single nucleotide variantPathogenicrs137852991GRCh37Chr 2, 44100948: 44100948
11ABCG8NM_022437.2(ABCG8): c.1787T> G (p.Leu596Arg)single nucleotide variantPathogenicrs137852992GRCh37Chr 2, 44104730: 44104730
12ABCG8NM_022437.2(ABCG8): c.691C> A (p.Pro231Thr)single nucleotide variantPathogenicrs137852993GRCh37Chr 2, 44079622: 44079622
13NM_022436.2(ABCG5): c.1222C> T (p.Arg408Ter)single nucleotide variantPathogenicrs119479065GRCh37Chr 2, 44051154: 44051154
14NM_022436.2(ABCG5): c.727C> T (p.Arg243Ter)single nucleotide variantPathogenicrs119479066GRCh37Chr 2, 44053568: 44053568
15NM_022436.2(ABCG5): c.1256G> A (p.Arg419His)single nucleotide variantPathogenicrs119479067GRCh37Chr 2, 44051120: 44051120
16NM_022436.2(ABCG5): c.1256G> C (p.Arg419Pro)single nucleotide variantPathogenicrs119479067GRCh37Chr 2, 44051120: 44051120
17NM_022436.2(ABCG5): c.1166G> A (p.Arg389His)single nucleotide variantPathogenicrs119480069GRCh37Chr 2, 44051210: 44051210
18NM_022436.2(ABCG5): c.229G> T (p.Glu77Ter)single nucleotide variantPathogenicrs119480070GRCh37Chr 2, 44065009: 44065009

Expression for genes affiliated with Sitosterolemia

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Search GEO for disease gene expression data for Sitosterolemia.

Pathways for genes affiliated with Sitosterolemia

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Pathways related to Sitosterolemia according to GeneCards Suite gene sharing:

(show all 11)
idSuper pathwaysScoreTop Affiliating Genes
1
Show member pathways
9.9ABCG5, ABCG8
29.5FDFT1, HMGCR
3
Show member pathways
9.3ABCG1, ABCG5, ABCG8
49.3ABCG1, ABCG5, CYP7A1
59.1ABCG5, ABCG8, CYP7A1, HMGCR
6
Show member pathways
9.0ACAT1, FDFT1, HMGCR
78.6ABCG5, ABCG8, APOB, MTTP
8
Show member pathways
8.6ACAT1, CYP7A1, FDFT1, HMGCR
9
Show member pathways
8.1ABCG1, ABCG5, ABCG8, APOB, MTTP
10
Show member pathways
7.3ABCG5, ABCG8, APOB, CYP7A1, FDFT1, HMGCR
11
Show member pathways
5.8ABCG1, ABCG5, ABCG8, ACAT1, APOB, CYP27A1

GO Terms for genes affiliated with Sitosterolemia

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Biological processes related to Sitosterolemia according to GeneCards Suite gene sharing:

(show all 8)
idNameGO IDScoreTop Affiliating Genes
1negative regulation of intestinal cholesterol absorptionGO:004579610.5ABCG5, ABCG8
2response to nutrientGO:000758410.0ABCG5, ABCG8
3phospholipid transportGO:00159149.7ABCG8, MTTP
4sterol metabolic processGO:00161259.6CYP27A1, CYP7A1
5lipid transportGO:00068699.4APOB, MTTP
6cholesterol homeostasisGO:00426329.4ABCG8, MTTP
7cholesterol effluxGO:00333449.2ABCG1, ABCG5, ABCG8, APOB
8cellular lipid metabolic processGO:00442559.1CYP7A1, FDFT1, HMGCR

Sources for Sitosterolemia

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2CDC
14ExPASy
15FDA
16FMA
24GTR
25HGMD
26HMDB
27ICD10
28ICD10 via Orphanet
29ICD9CM
30IUPHAR
31KEGG
34MedGen
36MeSH
37MESH via Orphanet
38MGI
41NCI
42NCIt
43NDF-RT
46NINDS
47Novoseek
49OMIM
50OMIM via Orphanet
54PubMed
55QIAGEN
60SNOMED-CT via Orphanet
64Tumor Gene Family of Databases
65UMLS
66UMLS via Orphanet