Cholesteryl ester storage disease (CESD) is a rare inherited disease that results from the accumulation of lipids in the body. It occurs due to a deficiency of an enzyme called lysosomal acid lipase (LAL or LIPA) enzyme, which is involved in lipid metabolism. The enzyme is responsible for the breakdown of lipids and cholesterol in the lysosomes, which are components of cells that carry out digestion of various substances.
The incidence of CESD is considered to be 1 in 40 000. Both genders, males as well as females are affected equally. The liver is the predominant organ that is affected, resulting in liver dysfunction. Complete absence of the enzyme results in a condition called Wolman disease. The affected babies usually die within 6 months of birth.
What are the Causes of Cholesteryl Ester Storage Disease?
As mentioned earlier, cholesteryl ester disease is a genetic disorder. It is caused by mutations in the lysosomal acid lipase (LIPA) gene located on chromosome 10.
Each of our cells has 23 pairs
of chromosomes. The child gets one set of 23 chromosomes from the mother, and another set from the father, which form the pairs.
CESD is an autosomal recessive disorder. For a person to develop CESD, the defective gene should be present on both chromosomes 10, the one obtained from the father as well as the one obtained from the mother. If the gene on only one chromosome 10 is defective, the person does not suffer from the condition but can pass it on to the next generation. Such individuals are called carriers.
The LIPA gene codes for the lysosomal acid lipase enzyme. This enzyme is responsible for the breakdown of fatty material, such as cholesteryl esters. When the enzyme function is reduced, these unbroken fatty materials accumulate in organs and tissues causing various effects on the body, such as increased cholesterol, enlarged liver, heart attack
, and stroke, among others.
What are the Symptoms and Signs of Cholesteryl Ester Storage Disease?
The symptoms of cholesteryl ester storage disease vary from individual to individual. Some people display symptoms in their childhood, while others do not display any symptoms; still others display detectable symptoms in their adulthood. The main features of CESD are enlisted below:
- Increased level of bad cholesterol
- Increased triglyceride levels
- Reduced levels of high-density lipoprotein, also known as the good cholesterol
- Abnormal lipid deposits in different organs
- Atherosclerosis of arteries, which could result in their block and could even cause heart attack and stroke
- Liver enlargement with fatty liver, liver fibrosis or even cirrhosis. The liver involvement could result in rupture of blood vessels at the base of the foodpipe which leads to severe and dangerous bleeding
- Occasional occurrence of enlarged adrenal glands, sometimes with calcification
How is Cholesteryl Ester Storage Disease Diagnosed?
The diagnosis of Cholesteryl Ester Storage Disease involves taking a medical history of the patient. The patientís family history is examined to assess any hereditary involvement. A physical examination detects familiar symptoms, such as an enlarged liver.
Since CESD is the result of a deficient lysosomal acid lipase enzyme, it is useful to perform tests to analyze the defective gene. Enzyme tests can analyze the levels of the LAL enzyme in the body. The concentration of the LAL enzyme is measured in circulating peripheral blood leukocytes.
An MRI scan is useful to detect the buildup of cholesteryl esters. Enlarged liver or hepatomegaly can be detected with a CT or computed tomography scan. The calcification of adrenal glands can be detected with radiological techniques.
How is Cholesteryl Ester Storage Disease Treated?
No specific treatment is present for CESD. The condition is treated with cholesterol reducing drugs, such as statins. Cholestyramine, fibrates, and ezetimibe can also be used to reduce cholesterol and triglyceride levels. A diet that is low in fats is also prescribed for the disease. When drugs and a low-fat diet
are combined together, it causes a reduction in the levels of triglycerides and cholesterol in the body. However, even these treatments do not appear to affect the outcome of the disease.Liver transplant
is recommended for those with badly affected livers. Liver transplants have been shown to be effective, though the procedure needs to be performed based on several factors, such as the age of the patient, the degree to which the liver is damaged, the health condition of the patient, among others.
Enzyme replacement therapy is being explored as treatment for CESD. Modified LAL enzyme introduced into the body could possibly perform the function that is compromised with the mutated enzyme. Gene therapy is also being tried out, where a normal gene is introduced into the cells, which can produce the LAL enzyme.
Since CESD is a genetically inherited condition, individuals who have a family history of the condition should consider genetic counselling
to understand the risk of transmitting the condition to their offspring.
People who already suffer from the condition should take medications along with a low fat diet.
Regular monitoring of the patient is necessary to diagnose and treat any manifestations early.