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Disease Profile

Lysosomal acid lipase deficiency

Prevalence
Prevalence estimates on Rare Medical Network websites are calculated based on data available from numerous sources, including US and European government statistics, the NIH, Orphanet, and published epidemiologic studies. Rare disease population data is recognized to be highly variable, and based on a wide variety of source data and methodologies, so the prevalence data on this site should be assumed to be estimated and cannot be considered to be absolutely correct.
1-9 / 100 000

3,310 - 29,790

US Estimated

1-9 / 100 000

5,135 - 46,215

Europe Estimated

Age of onset

Neonatal

ICD-10

E75.5

Inheritance

Autosomal dominant A pathogenic variant in only one gene copy in each cell is sufficient to cause an autosomal dominant disease

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Autosomal recessive Pathogenic variants in both copies of each gene of the chromosome are needed to cause an autosomal recessive disease and observe the mutant phenotype

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X-linked
dominant X-linked dominant inheritance, sometimes referred to as X-linked dominance, is a mode of genetic inheritance by which a dominant gene is carried on the X chromosome.

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X-linked
recessive Pathogenic variants in both copies of a gene on the X chromosome cause an X-linked recessive disorder

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Mitochondrial or multigenic Mitochondrial genetic disorders can be caused by changes (mutations) in either the mitochondrial DNA or nuclear DNA that lead to dysfunction of the mitochondria and inadequate production of energy.

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Multigenic or multifactor Inheritance involving many factors, of which at least one is genetic but none is of overwhelming importance, as in the causation of a disease by multiple genetic and environmental factors.

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Not applicable

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Other names (AKA)

LAL deficiency; LIPA deficiency

Summary

Lysosomal acid lipase deficiency is a metabolic lipid storage disease.[1][2] Two rare conditions may result from this deficiency (likely representing two ends of a clinical spectrum):[1][3]

  • Wolman disease: The early-onset and most severe form of the disease where lipids accumulate throughout the body, mostly in the liver, within the first weeks of life. Symptoms include an enlarged liver and spleen (hepatosplenomegaly), poor weight gain, a yellowish color of the skin and the whites of the eyes (jaundice), vomiting, diarrhea, fatty stool (steatorrhea), and poor absorption of nutrients from food (malabsorption), as well as calcium deposits in adrenal glands, anemia, liver disease (cirrhosis), and developmental delay. Infants with this form of lysosomal acid lipase deficiency develop failure in multiple organs, and severe malnutrition.
  • Cholesteryl ester storage disease: Less severe and starting later in life. Symptoms may include hepatosplenomegaly, liver disease (cirrhosis), and malabsorption with diarrhea, vomiting, and steatorrhea.

Lysosomal acid lipase deficiency is caused by mutations in the LIPA gene, which provides instructions to produce the lysosomal acid lipase enzyme. When there is not enough of this enzyme, the body cannot break down certain fats and this leads to a a toxic buildup of fatty substances in the body's cells and tissues.[1] Inheritance is autosomal recessive.[2][3] Enzyme replacement therapy for both Wolman disease and cholesteryl ester storage disease is currently approved for use in the United States, European Union, and Japan.[1]

Symptoms

This table lists symptoms that people with this disease may have. For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed. This information comes from a database called the Human Phenotype Ontology (HPO) . The HPO collects information on symptoms that have been described in medical resources. The HPO is updated regularly. Use the HPO ID to access more in-depth information about a symptom.

Medical Terms Other Names
Learn More:
HPO ID
80%-99% of people have these symptoms
Abdominal distention
Abdominal bloating
Abdominal swelling
Belly bloating
Bloating

[ more ]

0003270
Abdominal pain
Pain in stomach
Stomach pain

[ more ]

0002027
Adrenal calcification
0010512
Elevated alkaline phosphatase
Greatly elevated alkaline phosphatase
High serum alkaline phosphatase
Increased alkaline phosphatase
Increased serum alkaline phosphatase

[ more ]

0003155
Elevated hepatic transaminase
High liver enzymes
0002910
Fatal liver failure in infancy
0006583
Hepatic fibrosis
0001395
Hepatosplenomegaly
Enlarged liver and spleen
0001433
Hypercholesterolemia
Elevated serum cholesterol
Elevated total cholesterol
Increased total cholesterol

[ more ]

0003124
Hypertriglyceridemia
Increased plasma triglycerides
Increased serum triglycerides
Increased triglycerides

[ more ]

0002155
Jaundice
Yellow skin
Yellowing of the skin

[ more ]

0000952
Microvesicular hepatic steatosis
0001414
Steatorrhea
Fat in feces
0002570
Vacuolated lymphocytes
0001922
30%-79% of people have these symptoms
Coronary artery atherosclerosis
Plaque build-up in arteries supplying blood to heart
0001677
Diarrhea
Watery stool
0002014
Esophageal varix
Enlarged vein in esophagus
0002040
Precocious atherosclerosis
0004416
Stroke
0001297
Xanthelasma
Fatty deposits in skin around the eyes
Fatty deposits on eyelids

[ more ]

0001114
5%-29% of people have these symptoms
Abnormal urine potassium concentration
0012598
Acidosis
0001941
Anemia
Low number of red blood cells or hemoglobin
0001903
Ascites
Accumulation of fluid in the abdomen
0001541
Bone-marrow foam cells
0004333
Cachexia
Wasting syndrome
0004326
Dehydration
0001944
Failure to thrive
Faltering weight
Weight faltering

[ more ]

0001508
Feeding difficulties
Feeding problems
Poor feeding

[ more ]

0011968
Global developmental delay
0001263
Hyperkalemia
Elevated serum potassium levels
0002153
Hypernatriuria
0012605
Hypersplenism
0001971
Hyponatremia
Low blood sodium levels
0002902
Hypotension
Low blood pressure
0002615
Hypovolemia
Depleted blood volume
0011106
Malnutrition
0004395
Primary adrenal insufficiency
0008207
Pruritus
Itching
Itchy skin
Skin itching

[ more ]

0000989
Psychomotor deterioration
0002361
Pulmonary arterial hypertension
Increased blood pressure in blood vessels of lungs
0002092
Renal salt wasting
Loss of salt in urine
0000127
Vomiting
Throwing up
0002013
Percent of people who have these symptoms is not available through HPO
Autosomal recessive inheritance
0000007
Cirrhosis
Scar tissue replaces healthy tissue in the liver
0001394
Death in infancy
Infantile death
Lethal in infancy

[ more ]

0001522
Hepatic steatosis
Fatty infiltration of liver
Fatty liver

[ more ]

0001397
Hepatomegaly
Enlarged liver
0002240
Protuberant abdomen
Belly sticks out
Extended belly

[ more ]

0001538
Splenomegaly
Increased spleen size
0001744

Diagnosis

Making a diagnosis for a genetic or rare disease can often be challenging. Healthcare professionals typically look at a person’s medical history, symptoms, physical exam, and laboratory test results in order to make a diagnosis. The following resources provide information relating to diagnosis and testing for this condition. If you have questions about getting a diagnosis, you should contact a healthcare professional.

Testing Resources

  • The Genetic Testing Registry (GTR) provides information about the genetic tests for this condition. The intended audience for the GTR is health care providers and researchers. Patients and consumers with specific questions about a genetic test should contact a health care provider or a genetics professional.

    Treatment

    FDA-Approved Treatments

    The medication(s) listed below have been approved by the Food and Drug Administration (FDA) as orphan products for treatment of this condition. Learn more orphan products.

    Organizations

    Support and advocacy groups can help you connect with other patients and families, and they can provide valuable services. Many develop patient-centered information and are the driving force behind research for better treatments and possible cures. They can direct you to research, resources, and services. Many organizations also have experts who serve as medical advisors or provide lists of doctors/clinics. Visit the group’s website or contact them to learn about the services they offer. Inclusion on this list is not an endorsement by GARD.

    Learn more

    These resources provide more information about this condition or associated symptoms. The in-depth resources contain medical and scientific language that may be hard to understand. You may want to review these resources with a medical professional.

    Where to Start

      In-Depth Information

      • GeneReviews provides current, expert-authored, peer-reviewed, full-text articles describing the application of genetic testing to the diagnosis, management, and genetic counseling of patients with specific inherited conditions.
      • Medscape Reference provides information on this topic. You may need to register to view the medical textbook, but registration is free.
      • The Monarch Initiative brings together data about this condition from humans and other species to help physicians and biomedical researchers. Monarch’s tools are designed to make it easier to compare the signs and symptoms (phenotypes) of different diseases and discover common features. This initiative is a collaboration between several academic institutions across the world and is funded by the National Institutes of Health. Visit the website to explore the biology of this condition.
      • Online Mendelian Inheritance in Man (OMIM) is a catalog of human genes and genetic disorders. Each entry has a summary of related medical articles. It is meant for health care professionals and researchers. OMIM is maintained by Johns Hopkins University School of Medicine. 
      • Orphanet is a European reference portal for information on rare diseases and orphan drugs. Access to this database is free of charge.
      • PubMed is a searchable database of medical literature and lists journal articles that discuss Lysosomal acid lipase deficiency. Click on the link to view a sample search on this topic.

        References

        1. Acid Lipase Disease Information Page. National Institute of Neurological Disorders and Stroke (NINDS). https://www.ninds.nih.gov/Disorders/All-Disorders/Acid-Lipase-Disease-Information-Page. Accessed 12/6/2017.
        2. Lysosomal acid lipase deficiency. Orphanet. April 2014; https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=275761. Accessed 7/14/2015.
        3. Lysosomal Acid Lipase Deficiency. Online Mendelian Inheritance in Man (OMIM). December 17, 2013; https://www.omim.org/entry/278000. Accessed 7/14/2015.