Introduction
Apolipoprotein A1 deficiency is a monogenic metabolic rare disorder that results in undetectable Apo A-1 levels and HDL (high-density lipoprotein) cholesterol less than 20 mg/dl. It can be classified based on the type of affected gene and also the mutation. The effect of this deficiency can result in symptoms ranging from neural defects to optic defects. Apo-A1 deficiency can be prevented and treated as described in the article.
What Is Apo A-1?
Apo A-1 is a gene responsible for making apolipoprotein. It is the major component of HDL (high-density lipoprotein) cholesterol. It transports cholesterol and fats synthesized in the liver into circulation, picking up free cholesterol. HDL is good cholesterol, reducing the risk of heart and blood vessel diseases.
What Is the Classification for Apo A-1 Deficiency?
The classification of Apo A-1 deficiency is based on the type of genes affected and the type of mutation.
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Familial Apo A-1 Deficiency - It is a homozygous deletion mutation of the entire Apo A-1 gene complex where the patient suffers from severe cardiovascular disease. The plasma Apo A-1 is undetectable with low triglyceride and symptoms such as xanthomas and corneal arcus.
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Apo A-1 and Apo C3 Deficiency - The homozygous rearrangement of deoxyribonucleic acid (DNA) affects the Apo C3 and Apo A1 genes. As a result, these patients also show undetectable plasma Apo A1, including Apo C3, with symptoms like planar xanthomas and premature cardiovascular disease.
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Isolated Apo A-1 Deficiency - It is a homozygous Apo A-1 nonsense mutation in which Apo A-1 production is reduced. As a result, these patients show normal triglyceride levels and undetectable plasma Apo-A1 levels with symptoms such as bilateral retinopathy, spinocerebellar ataxia, bilateral cataract, and tendon xanthomas.
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Apo A-1 Variants - Apo A-1 variants are premature heterozygous frameshift mutations. Patients show low HDL levels and normal plasma lecithin-cholesterol acyltransferase (LCAT) activity. As a result, there is a risk of cardiovascular diseases. Heterozygous Apo- A1 missense mutations are also included in Apo-A1 variants showing low HDL and decreased LCAT activity with no risk of developing cardiovascular diseases. Few Apo-A1 variants show familial visceral amyloidosis.
What Are the Symptoms of Apo A-1 Deficiency?
Few patients are asymptomatic, and few develop symptoms such as-
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Cerebellar Ataxia - Poor muscle control due to disease or injury of the cerebellum (part of the brain) leading to clumsy movements like difficulty with balanced walking, eye movements, swallowing, and speech.
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Retinopathy - It is a disease of part of the eye (retina) that leads to loss or impairment of vision.
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Deafness - Hearing loss is usually a result of nerve or inner ear damage.
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Hepatomegaly - Increase in the size of the liver, which may or may not alter the normal function.
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Nephropathy - Declined kidney function leading to kidney failure.
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Corneal Opacities - A disorder of the part of the eye (cornea) which stops the passage of light through the retina leading to a clouded or scarred cornea.
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Coronary Arterial Disease - Narrowing or blockage of the heart's blood vessels.
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Cardiovascular Diseases - Diseases of the heart, including structural problems, diseased blood vessels, and blood clots, such as stroke.
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Endothelial Dysfunction - Slowing blood flow to the heart, causing chest pain and increased risk of heart conditions.
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Xanthelasma - It is a harmless yellowish soft or semi-solid bump near or on the eyelid.
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Xanthoma - The condition of the skin in which fat builds up under the skin's surface.
What Are the Mutations of Apo A-1?
There can be more than ten mutations, including deletion or insertion in the gene. It also includes the substitution of single amino acids. However, most mutations do not show their effect on HDL (high-density lipoprotein) concentration.
What Are the Types of Mutations of Apo A-1?
Mutations of Apo A-1 are divided into two distinct groups based on the location of the mutation.
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Group-1 - This group includes mutations in the terminal (end) part of the protein, and amyloidosis is associated with it.
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Group-2 - Mutations exist in the central region of the protein and affect the LCAT activity.
What Are the Diagnostic Methods for Apo A-1 Deficiency and Mutation of Apo A-1?
Diagnostic methods for gene deficiency and mutation specifically for the Apo A-1 gene are as follows:
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Blood investigations.
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Blood samples were collected after twelve hours fast to measure Apo A-1 levels.
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Lipid analysis.
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Single radial immunodiffusion.
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Two-dimensional gel electrophoresis of lipoproteins.
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Immunoblotting (sensitive and rapid assay for detection and characterization of proteins).
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DNA sequence analysis with PCR (polymerase chain reaction).
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LCAT (lecithin–cholesterol acyltransferase) activity test.
What Is the Treatment for Apo A-1 Deficiency?
Treatment includes medical therapy and surgical therapy.
Medical Therapy - Medical therapy includes administering drugs favoring the treatment outcome, such as:
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Statins - These are a group of medicines that help lower bad cholesterol in the blood. Side effects include muscle pain, increased blood sugar, and liver damage.
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Apo-A1 Infusion Therapy - Administration of exogenous Apo A-1 particles leading to increased HDL cholesterol levels show positive results; better treatment outcome was obtained using Apo A-1 gene transfer.
Surgical Therapy -
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Coronary Bypass Surgery - It is a surgery that creates a new direction for blood flow around a blocked or narrowed heart artery.
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Percutaneous Coronary Intervention (PCI) With Stent - It is a minimally invasive procedure that helps in opening up the blocked coronary arteries (blood vessels supplying the heart) using a stent (a hallowed tube maintaining the continuity of blood vessels).
Can Apo A1 Deficiency Be Prevented?
Early assessment of the symptoms and a proper diagnosis can prevent any disorder. Primary prevention includes high-intensity statin therapy, which aims at decreasing the level of LDL (low-density lipoprotein). Risk factors of cardiovascular diseases should be identified and addressed. Proper imaging technique to identify atherosclerosis helps in administering lipid-lowering therapy and also in the assessment of cardiovascular risk.
Conclusion
Any changes in the genes are called gene mutations. These mutations are inherited from the parents to offspring and cannot be prevented. The risks of such mutations can be prevented by following primary prevention steps. It is important to undergo diagnostic tests to detect the deficiency and mutation at the earliest possible and gain a better treatment outcome.
