LIPA

Lipase is an enzyme that catalyzes the breakdown of fats into fatty acids and glycerol, essential for fat digestion and absorption. 

Found in various tissues such as the liver, stomach, fat cells, blood vessels, and small intestine, lipases play crucial roles in lipid metabolism, cholesterol transport, cell signaling, and inflammation. 

Lysosomal acid lipase (LAL), encoded by the LIPA gene, is an essential enzyme that functions in lysosomes to break down lipids such as triglycerides and cholesteryl esters. 

LAL is important in intracellular lipid metabolism and homeostasis, with deficiency of this enzyme leading to rare genetic disorders like Wolman disease and cholesteryl ester storage disease characterized by lipid accumulation in various tissues.

LIPA is the gene that codes for LAL, and LIPA genetic mutations are associated with Wolman disease and cholesteryl ester storage disease. 

What is Lipase? [18.] 

Lipase is an enzyme that catalyzes the hydrolysis of fats (lipids), facilitating the breakdown of triglycerides into fatty acids and glycerol. This process is essential for the digestion and absorption of dietary fats as well as fat-soluble vitamins.

Lipases are also involved in cholesterol metabolism and are targeted by certain medications like orlistat, fibrates, and niacin to treat conditions related to fat digestion and cholesterol levels.

Locations of Lipase [18.] 

Lipases are found in various tissues, including the liver (hepatic lipase), stomach (gastric lipase), fat cells (hormone-sensitive lipase), blood vessels (lipoprotein lipase), and the small intestine (pancreatic lipase). 

Functions of Lipase

Functions of lipase may vary slightly depending on the type of lipase concerned. 

General functions of lipase include:

• Fat digestion: it catalyzes the breakdown of triglycerides into fatty acids and glycerol [6., 22.] 

• Lipid metabolism: helps in the processing and transport of dietary lipids [6., 22.] 

• Cell signaling: some lipases are involved in cell signaling pathways [6.] 

• Inflammation: certain lipases play a role in inflammatory processes [3., 8.] 

• Cholesterol transport: Lipoprotein lipase (LPL) plays a critical role in cholesterol metabolism by hydrolyzing triglycerides (TG) in lipoprotein particles, converting them into free fatty acids and glycerol. This process facilitates the uptake of these fatty acids into peripheral tissues for energy storage and consumption. [12., 22.] 

What Does the Enzyme Lysosomal Lipoprotein Lipase Do?

Lysosomal acid lipase regulates intracellular lipid stores. It is essential for the hydrolysis of cholesteryl esters and triglycerides in lysosomes.

It plays a crucial role in cellular cholesterol homeostasis and lipid metabolism.

This enzyme's normal functions are essential for regulating cholesterol metabolism and maintaining lipid homeostasis in various tissues, particularly in the liver, spleen, and macrophages. [4.] 

Deficiency of lysosomal acid lipase can cause Wolman disease in infants and cholesteryl ester storage disease in adults, both characterized by accumulation of lipids in various tissues. [4.] 

LIPA Deficiency Disorders

Lysosomal acid lipase (LIPA) is a crucial enzyme involved in the hydrolysis of cholesteryl esters and triglycerides within the lysosomal compartment. 

Deficiency of LIPA activity can lead to two distinct inherited metabolic disorders: Wolman disease and cholesteryl ester storage disease (CESD).

Wolman Disease [20.]

Wolman disease is a rare, severe lysosomal storage disorder characterized by the accumulation of cholesteryl esters and triglycerides in various tissues, particularly the liver, spleen, and intestinal mucosa. 

It is an autosomal recessive condition caused by mutations in the LIPA gene, resulting in a complete or near-complete absence of LIPA activity. 

Wolman disease presents in infancy with malabsorption, malnutrition, hepatomegaly, liver disease, and adrenal gland calcification leading to adrenal insufficiency. 

Without hematopoietic stem cell transplantation (HSCT), infants typically do not survive beyond one year. 

Diagnosis involves identifying biallelic pathogenic variants in the LIPA gene or deficient LAL enzyme activity. 

Enzyme replacement therapy with sebelipase alfa can be life-saving, and management includes nutritional support and treatment of adrenal insufficiency. 

Genetic counseling is essential as the disease is inherited in an autosomal recessive manner.

Cholesteryl Ester Storage Disease (CESD) [4.]

CESD is a milder form of LIPA deficiency disorder, also inherited in an autosomal recessive manner. 

Individuals with CESD have residual LIPA activity, leading to a slower accumulation of cholesteryl esters and triglycerides in various tissues. 

Clinical manifestations of CESD can vary widely, ranging from asymptomatic cases to severe liver disease, hyperlipidemia, and premature atherosclerosis. 

The onset of symptoms can occur at any age, and the disease course is generally less severe than Wolman disease.

What is a SNP?

A SNP, or single nucleotide polymorphism, refers to a variation at a single position in a gene along its DNA sequence.  A gene encodes a protein, so an alteration in that gene programs the production of an altered protein.  

As a type of protein with great functionality in human health, alterations in genes for enzymes may confer a difference in function of that enzyme.  The function of that enzyme may be increased or decreased, depending on the altered protein produced.  

SNPs are the most common type of genetic variation in humans and can occur throughout the genome, influencing traits, susceptibility to diseases, and response to medications.

The completion of the Human Genome Project has significantly expanded opportunities for genetic testing by providing a comprehensive map of the human genome that facilitates the identification of genetic variations associated with various health conditions, including identifying SNPs that may cause alterations in protein structure and function.  

Genetic testing for SNPs enables the identification of alterations in genes, shedding light on their implications in health and disease susceptibility.

Specific SNPs Associated with the LIPA Gene

E8SJM−1G>A 

The common E8SJM−1G>A mutation is prevalent in CESD. [5., 19.]

Laboratory Testing for LIPA

Genetic testing for single nucleotide polymorphisms (SNPs) typically involves obtaining a sample of DNA which can be extracted from blood, saliva, or cheek swabs. 

The sample may be taken in a lab, in the case of a blood sample.  Alternatively, a saliva or cheek swab sample may be taken from the comfort of home.  

Test Preparation

Prior to undergoing genetic testing, it's important to consult with a healthcare provider or genetic counselor to understand the purpose, potential outcomes, and implications of the test.  This consultation may involve discussing medical history, family history, and any specific concerns or questions. 

Additionally, individuals may be advised to refrain from eating, drinking, or chewing gum for a short period before providing a sample to ensure the accuracy of the test results.  Following sample collection, the DNA is processed in a laboratory where it undergoes analysis to identify specific genetic variations or SNPs. 

Once the testing is complete, individuals will typically receive their results along with interpretation and recommendations from a healthcare professional. 

It's crucial to approach genetic testing with proper understanding and consideration of its implications for one's health and well-being.

Patient-Centric Approaches

A patient-centered approach to SNP genetic testing emphasizes individualized medicine, tailoring healthcare decisions and interventions based on an individual's unique genetic makeup.

When that is combined with the individual’s health status and health history, preferences, and values, a truly individualized plan for care is possible. 

By integrating SNP testing into clinical practice, healthcare providers can offer personalized risk assessment, disease prevention strategies, and treatment plans that optimize patient outcomes and well-being. 

Genetic testing empowers a deeper understanding of genetic factors contributing to disease susceptibility, drug response variability, and overall health, empowering patients to actively participate in their care decisions. 

Furthermore, individualized medicine recognizes the importance of considering socioeconomic, cultural, and environmental factors alongside genetic information to deliver holistic and culturally sensitive care that aligns with patients' goals and preferences. 

Through collaborative decision-making and shared decision-making processes, patients and providers can make informed choices about SNP testing, treatment options, and lifestyle modifications, promoting patient autonomy, engagement, and satisfaction in their healthcare journey.

Genetic Panels and Combinations

Integrating multiple biomarkers into panels or combinations enhances the predictive power and clinical utility of pharmacogenomic testing. Biomarker panels comprising a variety of transporter proteins and enzymes including drug metabolizing enzymes offer comprehensive insights into individual drug response variability and treatment outcomes. 

Combining genetic SNP testing associated with drug transport, metabolism, and pharmacodynamics enables personalized medicine approaches tailored to individual patient characteristics and genetic profiles.

Order Genetic Testing

Click here to compare genetic test panels and order genetic testing for health-related SNPs.