Introduction:
The catabolism of fatty acids is known as the β-oxidation cycle. The abnormalities in fatty acid metabolism comprise the β-oxidation cycle defects. Medical literature has published that 20 defects in mitochondrial β-oxidation and fatty acid transportation lead to this disorder. The inheritance pattern of β-oxidation cycle defects is autosomal recessive, and the individual suffering from this disorder depicts a wide range of signs and symptoms during clinical examinations.
What Is Meant by β-Oxidation Cycle?
Molecular and biochemical pathways characterize fatty acid and mitochondrial β-oxidation cycles. This cycle has a significant role in maintaining energy homeostasis. Glucose, amino acids, and fatty acids are used as the substrate to maintain energy homeostasis. The β-oxidation cycle is the primary pathway for energy metabolism in the liver, heart, and skeletal muscles. When the individual is on fast or skips meals, the energy supply is maintained by the fatty acid and mitochondrial β-oxidation cycle. During such a situation, fats in the adipose tissues are utilized and converted into fatty acids. The fatty acid then released undergoes a mitochondrial β-oxidation cycle for energy release and utilization.
What Are β-Oxidation Cycle Defects?
The β-oxidation cycle comprises various steps in the pathways, and abnormality in any step can lead to a disorder. β-oxidation cycle defects are broadly classified into four groups:
TYPE 1: Defects associated with the entry of long-chain fatty acids into mitochondria are included in this type.
TYPE 2: An intramitochondrial defect in which the defect of long-chain fatty acid affects membrane-bound enzymes.
TYPE 3: Enzymes of the mitochondrial matrix are affected by β-oxidation defects in short and medium-chain fatty acids.
TYPE 4: Electron transfer defect associated with respiratory chain from mitochondrial β-oxidation defects.
Each defective step portrays different symptoms in individuals suffering from fatty acid and mitochondrial β-oxidation cycle disorder. Fatty acid disorders caused due to β-oxidation cycle defects result in insufficient energy release. Each defect has its clinical presentation, and a few of them are mentioned as follows:
Medium-Chain Acyl-CoA Dehydrogenase Deficiency (MADD): Genetic mutations result in the deficiency of this enzyme. It is most commonly noted in infants and toddlers. It is mainly present and associated with other defects and results in vomiting and reduced food intake and progresses into lethargy-like symptoms, dehydration, and decreased blood glucose level. If these signs and symptoms are not taken care of at the initial presentation, it can lead to brain edema and death of the child.
Very Long-Chain Acyl-Coa Dehydrogenase Deficiency (VLCADD): Deficiency of this enzyme can lead to death in the first few days. This deficiency is also associated with other heart-related disorders. Sometimes, the child may have a partial deficiency, and in such cases, heart-related conditions are noted in the child, along with symptoms of reduced blood sugar levels.
Carnitine Transport Disorders: Carnitine disorder is a three-step disorder, and the defect is caused due to defect in two enzymes, namely:
Carnitine palmitoyltransferase type 1 deficiency (CPT1D).
Carnitine-acylcarnitine translocase deficiency (CACTD).
In CPT1D cases, during early childhood, reduced blood sugar levels, functional liver defects, and rapidly progressing liver failure are commonly found signs and symptoms. Whereas in adults, symptoms of muscular and skeletal disorders are evident. The deficiency of this enzyme is related to a high infant mortality rate.
In CACTD cases, infant symptoms are more severe, including heart disorders comprising ventricular defects, seizures, reduced blood sugar levels, and sudden death. The prognosis is poor in such cases, and the diagnosis is based on DNA (deoxyribonucleic acid) sequencing.
What Are the Signs and Symptoms of β-Oxidation Cycle Defects?
Following are the few general features seen in the patient having β-oxidation cycle defects:
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The patient shows irritation in mood and change in behavior, and also child behaves highly lethargic.
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Heart disorders include heart enlargement and heart failure.
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Nausea, vomiting.
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Diarrhea.
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Decreased appetite.
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Decreased sugar level.
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Muscle weakness.
Specific clinical features are associated with the type of defect associated with the steps in the pathways of the β-oxidation cycle. Fasting or stress, insufficient diet intake due to β-oxidation cycle defects, and specific enzyme deficiencies can lead to fasting intolerance, muscle fatigue, decreased blood glucose level, liver failure, cardiac failure, coma, and death.
What Are the Tools Used to Diagnose β-Oxidation Cycle Defects?
Diagnosis of β-oxidation cycle defects can be made in 3 stages of an individual life:
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During the Prenatal Phase of Life- In this stage, biochemical and molecular methods are used for diagnosis. Samples are collected from villi in the placenta or through amniocentesis (amniotic fluid sampling using a wide bore needle to inspire the fluid). These samples collected are then checked for chromosomal abnormalities and mutations by DNA sequencing and other methods.
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Diagnosis in the Stage of Infancy or Toddler Stage- Blood spot profiling is the method of choice for diagnosing this defect during infancy. A small prick is done in the patient's fingers; the blood spots are collected as samples and used for genetic study. This helps analyze the type of enzyme deficiency or genetic mutation in an individual.
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During Childhood and Adulthood- The initial step in diagnosing at this stage of a patient's life includes complete blood count analysis, liver and kidney function test, specific enzyme testing, and urine analysis. These tests give the clinicians a basic idea of the stage and severity of the defect in that individual. According to the present laboratory findings, the patient can be advised for liver biopsy or other interventional diagnostic procedures.
What Treatment Protocols for Disorders Associated With β-Oxidation Cycle Defects?
Treatment choice depends upon the diagnosis stage of an individual's defect. Long-term therapy is prescribed in cases showing chronic symptoms, whereas acute patients are treated following emergency protocols. In acute cases, the primary goal of the treating doctor is reverse hypoglycemia (decreased blood sugar levels); once the glucose level is stabilized chances of a patient going into a coma get significantly reduced. For glucose level stabilization, 10 percent Dextrose is administered; medical literature advises 10 percent Dextrose at 2 ml/kg (milliliters per kilogram) in cases of neonates.
Long-term therapies target reducing fat breakdown (catabolism) by preventing the oxidation of fatty acids. A high carbohydrate diet is advised for such patients, and fatty food intake should be restricted. Other systemic illness is also noted and treated accordingly.
Conclusion:
Early diagnosis can prevent worsening symptoms in case of a patient suffering from β-oxidation cycle defects. Various genetic studies are undergoing to identify all genes involved with the causation of this defect.
