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Wolman disease(WOLD)

MedGen UID:
53088
Concept ID:
C0043208
Disease or Syndrome
Synonyms: Acid cholesteryl ester hydrolase deficiency, Wolman type; Acid lipase disease; CHOLESTEROL ESTER HYDROLASE DEFICIENCY, COMPLETE; LAL DEFICIENCY, COMPLETE; LIPA DEFICIENCY, COMPLETE; LYSOSOMAL ACID LIPASE DEFICIENCY, ACUTE INFANTILE; LYSOSOMAL ACID LIPASE DEFICIENCY, COMPLETE; WOLD; Wolman disease with hypolipoproteinemia and acanthocytosis; Wolman disease, CESD
SNOMED CT: Wolman's disease (82500001); Primary familial xanthomatosis with adrenal calcification (82500001); Familial visceral xanthomatosis (82500001); Deficiency of cholesterol esterase AND triacylglycerol lipase (82500001); Wolman xanthomatosis (82500001); Primary familial xanthomatosis (82500001); Wolman disease (82500001); Acid esterase deficiency (82500001); Acid lipase deficiency (82500001)
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:0019148
OMIM®: 620151
Orphanet: ORPHA75233

Definition

Deficiency of lysosomal acid lipase causes 2 distinct phenotypes in humans: Wolman disease (WOLD) and cholesteryl ester storage disease (CESD; 278000). 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]

Additional description

From MedlinePlus Genetics
Lysosomal acid lipase deficiency is an inherited condition characterized by problems with the breakdown and use of fats and cholesterol in the body (lipid metabolism). In affected individuals, harmful amounts of fats (lipids) accumulate in cells and tissues throughout the body, which typically causes liver disease. There are two forms of the condition. The most severe and rarest form begins in infancy. The less severe form can begin from childhood to late adulthood.

In the severe, early-onset form of lysosomal acid lipase deficiency, lipids accumulate throughout the body, particularly in the liver, within the first weeks of life. This accumulation of lipids leads to several health problems, including an enlarged liver and spleen (hepatosplenomegaly), poor weight gain, a yellow tint to the skin and the whites of the eyes (jaundice), vomiting, diarrhea, fatty stool (steatorrhea), and poor absorption of nutrients from food (malabsorption). In addition, affected infants often have calcium deposits in small hormone-producing glands on top of each kidney (adrenal glands), low amounts of iron in the blood (anemia), and developmental delay. Scar tissue quickly builds up in the liver, leading to liver disease (cirrhosis). Infants with this form of lysosomal acid lipase deficiency develop multi-organ failure and severe malnutrition and generally do not survive past 1 year.

In the later-onset form of lysosomal acid lipase deficiency, signs and symptoms vary and usually begin in mid-childhood, although they can appear anytime up to late adulthood. Nearly all affected individuals develop an enlarged liver (hepatomegaly); an enlarged spleen (splenomegaly) may also occur. About two-thirds of individuals have liver fibrosis, eventually leading to cirrhosis. Approximately one-third of individuals with the later-onset form have malabsorption, diarrhea, vomiting, and steatorrhea. Individuals with this form of lysosomal acid lipase deficiency may have increased liver enzymes and high cholesterol levels, which can be detected with blood tests.

Some people with this later-onset form of lysosomal acid lipase deficiency develop an accumulation of fatty deposits on the artery walls (atherosclerosis). Although these deposits are common in the general population, they usually begin at an earlier age in people with lysosomal acid lipase deficiency. The deposits narrow the arteries, increasing the chance of heart attack or stroke. The expected lifespan of individuals with later-onset lysosomal acid lipase deficiency depends on the severity of the associated health problems.

The two forms of lysosomal acid lipase deficiency were once thought to be separate disorders. The early-onset form was known as Wolman disease, and the later-onset form was known as cholesteryl ester storage disease. Although these two disorders have the same genetic cause and are now considered to be forms of a single condition, these names are still sometimes used to distinguish between the forms of lysosomal acid lipase deficiency.  https://medlineplus.gov/genetics/condition/lysosomal-acid-lipase-deficiency

Clinical features

From HPO
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.
Abdominal distention
MedGen UID:
34
Concept ID:
C0000731
Finding
Distention of the abdomen.
Hepatomegaly
MedGen UID:
42428
Concept ID:
C0019209
Finding
Abnormally increased size of the liver.
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.
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.
Splenomegaly
MedGen UID:
52469
Concept ID:
C0038002
Finding
Abnormal increased size of the spleen.
Fever
MedGen UID:
5169
Concept ID:
C0015967
Sign or Symptom
Body temperature elevated above the normal range.
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 calcification
MedGen UID:
78785
Concept ID:
C0271750
Disease or Syndrome
Calcification within the adrenal glands.

Term Hierarchy

Professional guidelines

PubMed

Mashima R, Takada S
Int J Mol Sci 2022 Dec 8;23(24) doi: 10.3390/ijms232415549. PMID: 36555187Free PMC Article
Paton DM
Drugs Today (Barc) 2016 May;52(5):287-93. doi: 10.1358/dot.2016.52.5.2488974. PMID: 27376161
Porto AF
Pediatr Endocrinol Rev 2014 Sep;12 Suppl 1:125-32. PMID: 25345094

Recent clinical studies

Etiology

Eskandari SK, Revenich EGM, Pot DJ, de Boer F, Bierings M, van Spronsen FJ, van Hasselt PM, Lindemans CA, Lubout CMA
N Engl J Med 2024 Feb 15;390(7):623-629. doi: 10.1056/NEJMoa2313398. PMID: 38354141
Li F, Zhang H
Arterioscler Thromb Vasc Biol 2019 May;39(5):850-856. doi: 10.1161/ATVBAHA.119.312136. PMID: 30866656Free 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
Paton DM
Drugs Today (Barc) 2016 May;52(5):287-93. doi: 10.1358/dot.2016.52.5.2488974. PMID: 27376161

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
Kanegane H, Noguchi A, Yamada Y, Yasumi T
Pediatr Int 2023 Jan-Dec;65(1):e15516. doi: 10.1111/ped.15516. PMID: 36843347
Pastores GM, Hughes DA
Drug Des Devel Ther 2020;14:591-601. Epub 2020 Feb 11 doi: 10.2147/DDDT.S149264. PMID: 32103901Free PMC Article
Porto AF
Pediatr Endocrinol Rev 2014 Sep;12 Suppl 1:125-32. PMID: 25345094
Tylki-Szymańska A, Jurecka A
Pril (Makedon Akad Nauk Umet Odd Med Nauki) 2014;35(1):99-106. PMID: 24798600

Therapy

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
Witeck CDR, Schmitz AC, de Oliveira JMD, Porporatti AL, De Luca Canto G, Pires MMS
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
Pastores GM, Hughes DA
Drug Des Devel Ther 2020;14:591-601. Epub 2020 Feb 11 doi: 10.2147/DDDT.S149264. PMID: 32103901Free PMC Article
Li F, Zhang H
Arterioscler Thromb Vasc Biol 2019 May;39(5):850-856. doi: 10.1161/ATVBAHA.119.312136. PMID: 30866656Free PMC Article
Porto AF
Pediatr Endocrinol Rev 2014 Sep;12 Suppl 1:125-32. PMID: 25345094

Prognosis

Zhao T, Liu S, Hanna NH, Jalal S, Ding X, Wan J, Yan C, Du H
J Immunother Cancer 2023 Mar;11(3) doi: 10.1136/jitc-2022-006272. PMID: 36914206Free PMC Article
Demaret T, Lacaille F, Wicker C, Arnoux JB, Bouchereau J, Belloche C, Gitiaux C, Grevent D, Broissand C, Adjaoud D, Abi Warde MT, Plantaz D, Bekri S, de Lonlay P, Brassier A
Orphanet J Rare Dis 2021 Dec 14;16(1):507. doi: 10.1186/s13023-021-02134-3. PMID: 34906190Free PMC Article
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
Krivit W, Freese D, Chan KW, Kulkarni R
Bone Marrow Transplant 1992;10 Suppl 1:97-101. PMID: 1521099

Clinical prediction guides

Balwani M, Balistreri W, D'Antiga L, Evans J, Ros E, Abel F, Wilson DP
Liver Int 2023 Jul;43(7):1537-1547. Epub 2023 May 24 doi: 10.1111/liv.15620. PMID: 37222260
Witeck CDR, Schmitz AC, de Oliveira JMD, Porporatti AL, De Luca Canto G, Pires MMS
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
Gomaraschi M, Bonacina F, Norata GD
Trends Pharmacol Sci 2019 Feb;40(2):104-115. Epub 2019 Jan 18 doi: 10.1016/j.tips.2018.12.006. PMID: 30665623
Aguisanda F, Yeh CD, Chen CZ, Li R, Beers J, Zou J, Thorne N, Zheng W
Orphanet J Rare Dis 2017 Jun 28;12(1):120. doi: 10.1186/s13023-017-0670-9. PMID: 28659158Free PMC Article
Fouchier SW, Defesche JC
Curr Opin Lipidol 2013 Aug;24(4):332-8. doi: 10.1097/MOL.0b013e328361f6c6. PMID: 23652569

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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