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Cholesteryl ester storage disease(CESD)

MedGen UID:
40266
Concept ID:
C0008384
Disease or Syndrome
Synonym: CESD
SNOMED CT: CESD - Cholesterol ester storage disease (57218003); Cholesterol ester storage disease (57218003)
Modes of inheritance:
Autosomal recessive inheritance
MedGen UID:
141025
Concept ID:
C0441748
Intellectual Product
Source: Orphanet
A mode of inheritance that is observed for traits related to a gene encoded on one of the autosomes (i.e., the human chromosomes 1-22) in which a trait manifests in individuals with two pathogenic alleles, either homozygotes (two copies of the same mutant allele) or compound heterozygotes (whereby each copy of a gene has a distinct mutant allele).
 
Gene (location): LIPA (10q23.31)
 
Monarch Initiative: MONDO:0019149
OMIM®: 278000
Orphanet: ORPHA75234

Definition

Deficiency of lysosomal acid lipase causes 2 distinct phenotypes in humans: Wolman disease (WOLD; 620151) and cholesteryl ester storage disease (CESD). WOLD is an early-onset fulminant disorder of infancy with massive infiltration of the liver, spleen, and other organs by macrophages filled with cholesteryl esters and triglycerides. Death occurs early in life. CESD is a milder, later-onset disorder with primary hepatic involvement by macrophages engorged with cholesteryl esters. This slowly progressive visceral disease has a wide spectrum of involvement ranging from early onset with severe cirrhosis to later onset of more slowly progressive hepatic disease with survival into adulthood (summary by Du et al., 2001). [from OMIM]

Clinical features

From HPO
Portal hypertension
MedGen UID:
9375
Concept ID:
C0020541
Disease or Syndrome
Increased pressure in the portal vein.
Hepatic foam cells
MedGen UID:
1814130
Concept ID:
C5558397
Finding
The presence of foam cells, a type of macrophage that localizes to fatty deposits on blood vessel walls, in the liver.
Failure to thrive
MedGen UID:
746019
Concept ID:
C2315100
Disease or Syndrome
Failure to thrive (FTT) refers to a child whose physical growth is substantially below the norm.
Diarrhea
MedGen UID:
8360
Concept ID:
C0011991
Sign or Symptom
Abnormally increased frequency (usually defined as three or more) loose or watery bowel movements a day.
Esophageal varix
MedGen UID:
5027
Concept ID:
C0014867
Disease or Syndrome
Extreme dilation of the submucusoal veins in the lower portion of the esophagus.
Hepatomegaly
MedGen UID:
42428
Concept ID:
C0019209
Finding
Abnormally increased size of the liver.
Hepatosplenomegaly
MedGen UID:
9225
Concept ID:
C0019214
Sign or Symptom
Simultaneous enlargement of the liver and spleen.
Cirrhosis of liver
MedGen UID:
7368
Concept ID:
C0023890
Disease or Syndrome
A chronic disorder of the liver in which liver tissue becomes scarred and is partially replaced by regenerative nodules and fibrotic tissue resulting in loss of liver function.
Steatorrhea
MedGen UID:
20948
Concept ID:
C0038238
Finding
Greater than normal amounts of fat in the feces. This is a result of malabsorption of lipids in the small intestine and results in frothy foul-smelling fecal matter that floats.
Vomiting
MedGen UID:
12124
Concept ID:
C0042963
Sign or Symptom
Forceful ejection of the contents of the stomach through the mouth by means of a series of involuntary spasmic contractions.
Liver failure
MedGen UID:
88444
Concept ID:
C0085605
Disease or Syndrome
A disorder characterized by the inability of the liver to metabolize chemicals in the body. Causes include cirrhosis and drug-induced hepatotoxicity. Signs and symptoms include jaundice and encephalopathy. Laboratory test results reveal abnormal plasma levels of ammonia, bilirubin, lactic dehydrogenase, and alkaline phosphatase.
Acute liver failure
MedGen UID:
58125
Concept ID:
C0162557
Disease or Syndrome
Hepatic failure refers to the inability of the liver to perform its normal synthetic and metabolic functions, which can result in coagulopathy and alteration in the mental status of a previously healthy individual. Hepatic failure is defined as acute if there is onset of encephalopathy within 8 weeks of the onset of symptoms in a patient with a previously healthy liver.
Hepatic fibrosis
MedGen UID:
116093
Concept ID:
C0239946
Disease or Syndrome
The presence of excessive fibrous connective tissue in the liver. Fibrosis is a reparative or reactive process.
Periportal fibrosis
MedGen UID:
337906
Concept ID:
C1849766
Disease or Syndrome
The presence of fibrosis affecting the interlobular stroma of liver.
Protuberant abdomen
MedGen UID:
340750
Concept ID:
C1854928
Finding
A thrusting or bulging out of the abdomen.
Hepatic steatosis
MedGen UID:
398225
Concept ID:
C2711227
Disease or Syndrome
Steatosis is a term used to denote lipid accumulation within hepatocytes.
Hepatic bridging fibrosis
MedGen UID:
868315
Concept ID:
C4022709
Disease or Syndrome
Hepatic fibrosis that reaches from a portal area to another portal area.
Increased hepatic echogenicity
MedGen UID:
1382460
Concept ID:
C4477000
Finding
Increased echogenicity of liver tissue on sonography, manifested as an increased amount of white on the screen of the sonography device.
Anemia
MedGen UID:
1526
Concept ID:
C0002871
Disease or Syndrome
A reduction in erythrocytes volume or hemoglobin concentration.
Disseminated intravascular coagulation
MedGen UID:
41620
Concept ID:
C0012739
Disease or Syndrome
Disseminated intravascular coagulation is characterized by the widespread activation of coagulation, which results in the intravascular formation of fibrin and ultimately thrombotic occlusion of small and midsize vessels.
Thrombocytopenia
MedGen UID:
52737
Concept ID:
C0040034
Disease or Syndrome
A reduction in the number of circulating thrombocytes.
Hypersplenism
MedGen UID:
9372
Concept ID:
C0020532
Disease or Syndrome
A malfunctioning of the spleen in which it prematurely destroys red blood cells.
Leukopenia
MedGen UID:
6073
Concept ID:
C0023530
Disease or Syndrome
An abnormal decreased number of leukocytes in the blood.
Splenomegaly
MedGen UID:
52469
Concept ID:
C0038002
Finding
Abnormal increased size of the spleen.
Bone-marrow foam cells
MedGen UID:
383940
Concept ID:
C1856560
Finding
The presence of foam cells in the bone marrow, generally demonstrated by bone-marrow aspiration or biopsy. Foam cells have a vacuolated appearance due to the presence of complex lipid deposits, giving them a foamy or soap-suds appearance.
Hypercholesterolemia
MedGen UID:
5687
Concept ID:
C0020443
Disease or Syndrome
An increased concentration of cholesterol in the blood.
Decreased HDL cholesterol concentration
MedGen UID:
57731
Concept ID:
C0151691
Finding
An decreased concentration of high-density lipoprotein cholesterol in the blood.
Elevated circulating aspartate aminotransferase concentration
MedGen UID:
57497
Concept ID:
C0151904
Finding
The concentration of aspartate aminotransferase (AST) in the blood circulation is above the upper limit of normal.
Elevated circulating alanine aminotransferase concentration
MedGen UID:
57740
Concept ID:
C0151905
Finding
An abnormally high concentration in the circulation of alanine aminotransferase (ALT).
Increased LDL cholesterol concentration
MedGen UID:
154289
Concept ID:
C0549399
Finding
An elevated concentration of low-density lipoprotein cholesterol in the blood.
Hypertriglyceridemia
MedGen UID:
167238
Concept ID:
C0813230
Finding
An abnormal increase in the level of triglycerides in the blood.
Low alkaline phosphatase
MedGen UID:
349734
Concept ID:
C1860130
Finding
Abnormally reduced serum levels of alkaline phosphatase.
Elevated gamma-glutamyltransferase level
MedGen UID:
1370086
Concept ID:
C4476869
Finding
Increased level of the enzyme gamma-glutamyltransferase (GGT). GGT is mainly present in kidney, liver, and pancreatic cells, but small amounts are present in other tissues.
Increased circulating lactate dehydrogenase concentration
MedGen UID:
1377250
Concept ID:
C4477095
Finding
An elevated level of the enzyme lactate dehydrogenase in the blood circulation.
Reduced lysosomal acid lipase activity
MedGen UID:
1620002
Concept ID:
C4531280
Finding
Reduction in the activity of lysosomal acid lipase (LAL) in the blood. Lysosomal lipase activity is measured. LAL hydrolyzes cholesteryl esters derived from cell internalization of plasma lipoproteins.
Adrenal insufficiency
MedGen UID:
1351
Concept ID:
C0001623
Disease or Syndrome
Insufficient production of steroid hormones (primarily cortisol) by the adrenal glands.
Adrenal calcification
MedGen UID:
78785
Concept ID:
C0271750
Disease or Syndrome
Calcification within the adrenal glands.

Professional guidelines

PubMed

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Nascimbeni F, Dionisi Vici C, Vespasiani Gentilucci U, Angelico F, Nobili V, Petta S, Valenti L; AISF Rare Diseases Committee
Dig Liver Dis 2020 Apr;52(4):359-367. Epub 2020 Jan 2 doi: 10.1016/j.dld.2019.12.005. PMID: 31902560
Paton DM
Drugs Today (Barc) 2016 May;52(5):287-93. doi: 10.1358/dot.2016.52.5.2488974. PMID: 27376161

Recent clinical studies

Etiology

Nascimbeni F, Dionisi Vici C, Vespasiani Gentilucci U, Angelico F, Nobili V, Petta S, Valenti L; AISF Rare Diseases Committee
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Li F, Zhang H
Arterioscler Thromb Vasc Biol 2019 May;39(5):850-856. doi: 10.1161/ATVBAHA.119.312136. PMID: 30866656Free PMC Article
Zhang H
Curr Opin Lipidol 2018 Jun;29(3):218-223. doi: 10.1097/MOL.0000000000000507. PMID: 29547398Free PMC Article
Vázquez-Frias R, García-Ortiz JE, Valencia-Mayoral PF, Castro-Narro GE, Medina-Bravo PG, Santillán-Hernández Y, Flores-Calderón J, Mehta R, Arellano-Valdés CA, Carbajal-Rodríguez L, Navarrete-Martínez JI, Urbán-Reyes ML, Valadez-Reyes MT, Zárate-Mondragón F, Consuelo-Sánchez A
Rev Gastroenterol Mex (Engl Ed) 2018 Jan-Mar;83(1):51-61. Epub 2017 Dec 27 doi: 10.1016/j.rgmx.2017.08.001. PMID: 29287906
Maciejko JJ
Am J Cardiovasc Drugs 2017 Jun;17(3):217-231. doi: 10.1007/s40256-017-0216-5. PMID: 28197978

Diagnosis

Korbelius M, Kuentzel KB, Bradić I, Vujić N, Kratky D
Trends Mol Med 2023 Jun;29(6):425-438. Epub 2023 Apr 5 doi: 10.1016/j.molmed.2023.03.001. PMID: 37028992Free PMC Article
Pericleous M, Kelly C, Wang T, Livingstone C, Ala A
Lancet Gastroenterol Hepatol 2017 Sep;2(9):670-679. doi: 10.1016/S2468-1253(17)30052-3. PMID: 28786388
Pant M, Oshima K
Ann Diagn Pathol 2017 Dec;31:66-70. Epub 2017 Feb 9 doi: 10.1016/j.anndiagpath.2017.02.005. PMID: 28318950
Tylki-Szymańska A, Jurecka A
Pril (Makedon Akad Nauk Umet Odd Med Nauki) 2014;35(1):99-106. PMID: 24798600
Zhang B, Porto AF
J Pediatr Gastroenterol Nutr 2013 Jun;56(6):682-5. doi: 10.1097/MPG.0b013e31828b36ac. PMID: 23403440

Therapy

Korbelius M, Kuentzel KB, Bradić I, Vujić N, Kratky D
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Li F, Zhang H
Arterioscler Thromb Vasc Biol 2019 May;39(5):850-856. doi: 10.1161/ATVBAHA.119.312136. PMID: 30866656Free PMC Article
Frampton JE
Am J Cardiovasc Drugs 2016 Dec;16(6):461-468. doi: 10.1007/s40256-016-0203-2. PMID: 27878737
Bernstein DL, Hülkova H, Bialer MG, Desnick RJ
J Hepatol 2013 Jun;58(6):1230-43. Epub 2013 Feb 26 doi: 10.1016/j.jhep.2013.02.014. PMID: 23485521

Prognosis

Zhang JH, Lin AP, Zhang L, Ruan DD, Gao MZ, Chen Q, Yu HP, Liao LS, Lin XF, Fang ZT, Lin F, Lu SY, Luo JW, Zheng XL, Chen MS
Dig Dis Sci 2024 Jun;69(6):2109-2122. Epub 2024 Apr 2 doi: 10.1007/s10620-024-08395-9. PMID: 38564148
Pant M, Oshima K
Ann Diagn Pathol 2017 Dec;31:66-70. Epub 2017 Feb 9 doi: 10.1016/j.anndiagpath.2017.02.005. PMID: 28318950
Reiner Ž, Guardamagna O, Nair D, Soran H, Hovingh K, Bertolini S, Jones S, Ćorić M, Calandra S, Hamilton J, Eagleton T, Ros E
Atherosclerosis 2014 Jul;235(1):21-30. Epub 2014 Apr 15 doi: 10.1016/j.atherosclerosis.2014.04.003. PMID: 24792990
Freudenberg F, Bufler P, Ensenauer R, Lohse P, Koletzko S
Z Gastroenterol 2013 Oct;51(10):1184-7. Epub 2013 Oct 11 doi: 10.1055/s-0033-1350463. PMID: 24122380
Du H, Sheriff S, Bezerra J, Leonova T, Grabowski GA
Mol Genet Metab 1998 Jun;64(2):126-34. doi: 10.1006/mgme.1998.2707. PMID: 9705237

Clinical prediction guides

Zhang JH, Lin AP, Zhang L, Ruan DD, Gao MZ, Chen Q, Yu HP, Liao LS, Lin XF, Fang ZT, Lin F, Lu SY, Luo JW, Zheng XL, Chen MS
Dig Dis Sci 2024 Jun;69(6):2109-2122. Epub 2024 Apr 2 doi: 10.1007/s10620-024-08395-9. PMID: 38564148
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J Pediatr (Rio J) 2022 Jan-Feb;98(1):4-14. Epub 2021 May 6 doi: 10.1016/j.jped.2021.03.003. PMID: 33964214Free PMC Article
Yvan-Charvet L, Bonacina F, Guinamard RR, Norata GD
Cardiovasc Res 2019 Jul 1;115(9):1393-1407. doi: 10.1093/cvr/cvz127. PMID: 31095280
Lipiński P, Ługowska A, Zakharova EY, Socha P, Tylki-Szymańska A
J Pediatr Gastroenterol Nutr 2018 Oct;67(4):452-457. doi: 10.1097/MPG.0000000000002084. PMID: 29958253
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J Hepatol 2013 Jun;58(6):1230-43. Epub 2013 Feb 26 doi: 10.1016/j.jhep.2013.02.014. PMID: 23485521

Recent systematic reviews

Carter A, Brackley SM, Gao J, Mann JP
J Hepatol 2019 Jan;70(1):142-150. Epub 2018 Oct 11 doi: 10.1016/j.jhep.2018.09.028. PMID: 30315827

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