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Lysosomal acid lipase deficiency(CESD)

MedGen UID:
53088
Concept ID:
C0043208
Disease or Syndrome
Synonyms: CHOLESTEROL ESTER HYDROLASE DEFICIENCY; Cholesteryl ester storage disease; LAL DEFICIENCY; Wolman Disease
Modes of inheritance:
Autosomal recessive inheritance
MedGen UID:
141025
Concept ID:
C0441748
Intellectual Product
Sources: HPO, OMIM, 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 homozygotes. In the context of medical genetics, autosomal recessive disorders manifest in homozygotes (with two copies of the mutant allele) or compound heterozygotes (whereby each copy of a gene has a distinct mutant allele).
Autosomal recessive inheritance (HPO, OMIM, Orphanet)
SNOMED CT: Wolman's disease (82500001); Primary familial xanthomatosis with adrenal calcification (82500001); Familial visceral xanthomatosis (82500001); LIPA deficiency (82500001); Lysosomal acid lipase deficiency (82500001); Deficiency of cholesterol esterase AND triacylglycerol lipase (82500001); Wolman xanthomatosis (82500001); Primary familial xanthomatosis (82500001); LAL (Lysosomal acid lipase) deficiency (715923003); Lysosomal acid lipase deficiency (715923003); LALD - Lysosomal acid lipase deficiency (715923003); Xanthomatosis, familial (238074007); Wolman disease (82500001); Acid esterase deficiency (82500001); Acid lipase deficiency (82500001)
 
Gene (location): LIPA (10q23.31)
OMIM®: 278000
Orphanet: ORPHA75233

Definition

Deficiency of lysosomal acid lipase causes 2 distinct phenotypes in humans: Wolman disease and cholesteryl ester storage disease (CESD). Wolman disease 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. Wolman disease is very rare, with an incidence of less than one in 100,000 live births. CESD is a milder, later-onset disorder with primary hepatic involvement by macrophages engorged with cholesteryl esters. This slowly progressive visceral disease has a very 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 GHR
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://ghr.nlm.nih.gov/condition/lysosomal-acid-lipase-deficiency

Clinical features

Pulmonary arterial hypertension
MedGen UID:
468368
Concept ID:
C3203102
Disease or Syndrome
Pulmonary hypertension is defined mean pulmonary artery pressure of 25mmHg or more and pulmonary capillary wedge pressure of 15mmHg or less when measured by right heart catheterisation at rest and in a supine position.
Adrenal calcification
MedGen UID:
78785
Concept ID:
C0271750
Disease or Syndrome
Calcification within the adrenal glands.
Failure to thrive
MedGen UID:
115900
Concept ID:
C0231246
Finding
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
Diarrhea means that you have loose, watery stools more than three times in one day. You may also have cramps, bloating, nausea and an urgent need to have a bowel movement. . Causes of diarrhea include bacteria, viruses or parasites, certain medicines, food intolerances and diseases that affect the stomach, small intestine or colon. In many cases, no cause can be found. . Although usually not harmful, diarrhea can become dangerous or signal a more serious problem. You should talk to your doctor if you have a strong pain in your abdomen or rectum, a fever, blood in your stools, severe diarrhea for more than three days or symptoms of dehydration. If your child has diarrhea, do not hesitate to call the doctor for advice. Diarrhea can be dangerous in children. . NIH: National Institute of Diabetes and Digestive and Kidney Diseases.
Esophageal varix
MedGen UID:
5027
Concept ID:
C0014867
Finding
Extreme dilation of the submucusoal veins in the lower portion of the esophagus.
Hepatosplenomegaly
MedGen UID:
9225
Concept ID:
C0019214
Sign or Symptom
Simultaneous enlargement of the liver and spleen.
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.
Pulmonary arterial hypertension
MedGen UID:
468368
Concept ID:
C3203102
Disease or Syndrome
Pulmonary hypertension is defined mean pulmonary artery pressure of 25mmHg or more and pulmonary capillary wedge pressure of 15mmHg or less when measured by right heart catheterisation at rest and in a supine position.
Vacuolated lymphocytes
MedGen UID:
332307
Concept ID:
C1836855
Finding
The presence of clear, sharply defined vacuoles in the lymphocyte cytoplasm.
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.
Adrenal calcification
MedGen UID:
78785
Concept ID:
C0271750
Disease or Syndrome
Calcification within the adrenal glands.

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • CROGVLysosomal acid lipase deficiency
Follow this link to review classifications for Lysosomal acid lipase deficiency in Orphanet.

Suggested Reading

PubMed

Shirley M
Drugs 2015 Nov;75(16):1935-40. doi: 10.1007/s40265-015-0479-6. PMID: 26452566

Recent clinical studies

Etiology

Paton DM
Drugs Today (Barc) 2016 May;52(5):287-93. doi: 10.1358/dot.2016.52.5.2488974. PMID: 27376161
Burton BK, Balwani M, Feillet F, Barić I, Burrow TA, Camarena Grande C, Coker M, Consuelo-Sánchez A, Deegan P, Di Rocco M, Enns GM, Erbe R, Ezgu F, Ficicioglu C, Furuya KN, Kane J, Laukaitis C, Mengel E, Neilan EG, Nightingale S, Peters H, Scarpa M, Schwab KO, Smolka V, Valayannopoulos V, Wood M, Goodman Z, Yang Y, Eckert S, Rojas-Caro S, Quinn AG
N Engl J Med 2015 Sep 10;373(11):1010-20. doi: 10.1056/NEJMoa1501365. PMID: 26352813
Burton BK, Deegan PB, Enns GM, Guardamagna O, Horslen S, Hovingh GK, Lobritto SJ, Malinova V, McLin VA, Raiman J, Di Rocco M, Santra S, Sharma R, Sykut-Cegielska J, Whitley CB, Eckert S, Valayannopoulos V, Quinn AG
J Pediatr Gastroenterol Nutr 2015 Dec;61(6):619-25. doi: 10.1097/MPG.0000000000000935. PMID: 26252914Free PMC Article
Sadhukhan M, Saha A, Vara R, Bhaduri B
BMJ Case Rep 2014 May 15;2014 doi: 10.1136/bcr-2013-202652. PMID: 24832708Free PMC Article
Thelwall PE, Smith FE, Leavitt MC, Canty D, Hu W, Hollingsworth KG, Thoma C, Trenell MI, Taylor R, Rutkowski JV, Blamire AM, Quinn AG
J Hepatol 2013 Sep;59(3):543-9. Epub 2013 Apr 25 doi: 10.1016/j.jhep.2013.04.016. PMID: 23624251Free PMC Article

Diagnosis

Ivashkin V, Zharkova M
N Engl J Med 2017 Mar 2;376(9):e14. doi: 10.1056/NEJMicm1610060. PMID: 28249129
Frampton JE
Am J Cardiovasc Drugs 2016 Dec;16(6):461-468. doi: 10.1007/s40256-016-0203-2. PMID: 27878737
Burton BK, Deegan PB, Enns GM, Guardamagna O, Horslen S, Hovingh GK, Lobritto SJ, Malinova V, McLin VA, Raiman J, Di Rocco M, Santra S, Sharma R, Sykut-Cegielska J, Whitley CB, Eckert S, Valayannopoulos V, Quinn AG
J Pediatr Gastroenterol Nutr 2015 Dec;61(6):619-25. doi: 10.1097/MPG.0000000000000935. PMID: 26252914Free PMC Article
Pajares S, Arias A, García-Villoria J, Macías-Vidal J, Ros E, de las Heras J, Girós M, Coll MJ, Ribes A
J Lipid Res 2015 Oct;56(10):1926-35. Epub 2015 Aug 3 doi: 10.1194/jlr.M060343. PMID: 26239048Free PMC Article
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

Therapy

Frampton JE
Am J Cardiovasc Drugs 2016 Dec;16(6):461-468. doi: 10.1007/s40256-016-0203-2. PMID: 27878737
Med Lett Drugs Ther 2016 Sep 26;58(1504):e126-7. PMID: 27649344
Paton DM
Drugs Today (Barc) 2016 May;52(5):287-93. doi: 10.1358/dot.2016.52.5.2488974. PMID: 27376161
Burton BK, Balwani M, Feillet F, Barić I, Burrow TA, Camarena Grande C, Coker M, Consuelo-Sánchez A, Deegan P, Di Rocco M, Enns GM, Erbe R, Ezgu F, Ficicioglu C, Furuya KN, Kane J, Laukaitis C, Mengel E, Neilan EG, Nightingale S, Peters H, Scarpa M, Schwab KO, Smolka V, Valayannopoulos V, Wood M, Goodman Z, Yang Y, Eckert S, Rojas-Caro S, Quinn AG
N Engl J Med 2015 Sep 10;373(11):1010-20. doi: 10.1056/NEJMoa1501365. PMID: 26352813
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

Prognosis

Gómez-Nájera M, Barajas-Medina H, Gallegos-Rivas MC, Mendez-Sashida P, Goss KA, Sims KB, Tripuraneni R, Valles-Ayoub Y
J Pediatr Gastroenterol Nutr 2015 Mar;60(3):e22-4. doi: 10.1097/MPG.0000000000000175. PMID: 24048164
Sadhukhan M, Saha A, Vara R, Bhaduri B
BMJ Case Rep 2014 May 15;2014 doi: 10.1136/bcr-2013-202652. PMID: 24832708Free PMC Article
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
Lee TM, Welsh M, Benhamed S, Chung WK
Mol Genet Metab 2011 Dec;104(4):703-5. Epub 2011 Sep 14 doi: 10.1016/j.ymgme.2011.09.006. PMID: 21963785Free PMC Article

Clinical prediction guides

Burton BK, Balwani M, Feillet F, Barić I, Burrow TA, Camarena Grande C, Coker M, Consuelo-Sánchez A, Deegan P, Di Rocco M, Enns GM, Erbe R, Ezgu F, Ficicioglu C, Furuya KN, Kane J, Laukaitis C, Mengel E, Neilan EG, Nightingale S, Peters H, Scarpa M, Schwab KO, Smolka V, Valayannopoulos V, Wood M, Goodman Z, Yang Y, Eckert S, Rojas-Caro S, Quinn AG
N Engl J Med 2015 Sep 10;373(11):1010-20. doi: 10.1056/NEJMoa1501365. PMID: 26352813
Thelwall PE, Smith FE, Leavitt MC, Canty D, Hu W, Hollingsworth KG, Thoma C, Trenell MI, Taylor R, Rutkowski JV, Blamire AM, Quinn AG
J Hepatol 2013 Sep;59(3):543-9. Epub 2013 Apr 25 doi: 10.1016/j.jhep.2013.04.016. PMID: 23624251Free PMC Article
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
Guénard F, Houde A, Bouchard L, Tchernof A, Deshaies Y, Biron S, Lescelleur O, Biertho L, Marceau S, Pérusse L, Vohl MC
Obesity (Silver Spring) 2012 Oct;20(10):2075-82. Epub 2012 Mar 7 doi: 10.1038/oby.2012.52. PMID: 22395809
Desai PK, Astrin KH, Thung SN, Gordon RE, Short MP, Coates PM, Desnick RJ
Am J Med Genet 1987 Mar;26(3):689-98. doi: 10.1002/ajmg.1320260324. PMID: 3565483

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