Introduction:
Gamma hydroxybutyric acidemia is a rare inborn metabolic disorder, and medical literature has very few reported cases of individuals affected by the enzyme deficiency genetic disorder. Organic acidemia is a condition where the toxic build-up of particular acids, like organic acids, occurs in the blood. γ-hydroxybutyric acidemia is an important enzyme that is responsible for the metabolism of the amino acid valine. Due to the lack of valine breakdown, toxic compounds build up inside the body of the individual suffering from a deficiency of the γ-hydroxybutyric enzyme. The accumulation of toxins is majorly found inside the mitochondria (the cell's powerhouse). γ-hydroxybutyric acidemia can cause difficulty feeding, poor muscle tone, frequent seizures, and delayed intellectual status. This deficiency disorder has an autosomal recessive inheritance pattern. Individuals suffering from γ-hydroxybutyric acidemia have clinical features similar to a disorder called a 4-hydroxybutyric acid deficiency.
Can a Child Get Gamma-Hydroxybutyric Acidemia From Their Parents?
γ-hydroxybutyric acidemiais an inherited genetic disorder with an autosomal recessive inheritance pattern. This means that both the parents, the mother and the father of the individual affected by γ-hydroxybutyric acidemia, carry the defective genes. Still, the parents do not show the symptoms of the disease. Genetic mutations (structural changes in the genes) are associated with γ-hydroxybutyric acidemia. There is a twenty-five percent chance or probability that parent carriers of the defective gene will have children with γ-hydroxybutyric acidemia. Genetic mapping in the prenatal stage can help doctors analyze the likelihood of the child suffering from γ-hydroxybutyric acidemia.
What Is Organic Acidemia?
Organic acidemia describes a group of disorders characterized by increased levels of organic acids in the blood. It is caused due to altered functioning of the protein breakdown procedures. Dysfunctional protein breakdown is related to deficient enzymatic activity involved in the protein breakdown procedure. As a result, the end product of these organic protein breakdown pathways gets reduced, leading to deficiency of particular amino acids and increased acidic byproducts leading to the high acid content of the urine excreted in the individuals affected by such disorders.
What Are the Signs and Symptoms of Gamma-Hydroxybutyric Acidemia?
The features of γ-hydroxybutyric acidemia can be noted at birth or in the early days of infancy. A few common signs and symptoms reported in infants suffering from γ-hydroxybutyric acidemia are as follows:
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The infant refuses to get fed. The reduction in dietary intake leads to growth retardation and irritability in the child.
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The child faces difficulty digesting food due to increased acidity, resulting in frequent vomiting.
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Increased acidic levels and frequent vomiting lead to water loss from the body causing dehydration in infants.
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Reduced levels of neutrophils in the blood lead to increased susceptibility to infections. Infections, including fungal, viral, and bacterial, are frequently noted in infants due to decreased immune system activity.
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It explains the reduced glucose levels in infants. Hypoglycemia causes lethargy and disinterest in playing. The infants are often irritated and keep crying, which is hard to calm.
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In a few infants, seizures are commonly noted. When the child gets seizures, the parent's responsibility is to protect them from getting hurt.
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In severe, complicated cases, the lethargy noted in the infant can progress to a coma. It is a life-threatening situation; proper medical guidance is required to protect the child at this stage.
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Pancreatitis (pancreas infection leading to inflammation) is another life-threatening infection in these individuals.
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Critical care is required to prevent these complications from worsening.
How Can Organic Acidemia Be Diagnosed?
Following are a few diagnostic tests that help the doctor diagnose conditions like organic Acidemia:
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Blood Sugar Levels: Individuals suffering from organic acidemia generally show reduced glucose levels (hypoglycemia). Medical research papers have depicted that In infants, the glucose level is around 40 mg/dl (milligrams per deciliter), 60 mg/dl in children, and approximately 75 mg/dl in children above 16.
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Tests to Analyze Neutrophil Levels: Neutropenia is a common feature that depicts reduced levels of neutrophils in the blood. Medical research papers state neutrophil levels to be approximately 1500 cells per cubic millimeter of blood. White blood cell levels can vary in age groups; slight value changes are also noted in reports from other laboratories; therefore, these points should be noted before concluding.
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Liver Function Tests: It is done to check for protein metabolism activities. In cases of organic acidemia, liver function tests tend to depict abnormal values.
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Radiographic Diagnosis: Radiographic tests like magnetic resonance imaging (MRI) and computed tomography (CT) helps in analyzing the causes of seizures and headaches in patients. It can help doctors differentiate the cause of seizures, migraine, and common headaches between enzyme deficiency disorders or any lesion in the brain.
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Genetic Mapping: Genetic mapping helps identify the genetic defect responsible for the causation of 3-hydroxyisobutyryl-CoA deacylase enzyme deficiency disorder. Various research is ongoing to identify the specific gene responsible for the disorder.
What Are the Management Protocols for Organic Acidemia?
The fundamental motive of the management protocols is to save the individual from life-threatening situations. Symptoms like vomiting and dehydration should be monitored carefully, and electrolyte replacements should be done to treat such medical conditions. Parents should be aware of the child's conditions, and preventive measures and diet plans should be given to control the acidic levels. The surgical approach is the treatment of choice in severe complicated conditions like heart enlargement. Future modifications focus on using genome-wide association studies as a genomic medicine for treating and preventing various enzyme deficiency-associated metabolic diseases and cancers.
Following are the few changes or new ideas being imposed at present to brighten the future of the management of genetic disorders:
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Development of statistical variants that can detect even rare alleles without any bias.
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It is improving the database search engine to easily assess the required genomic sequence information.
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Standard mathematical formulations are being developed to set a genome-wide significant threshold, reducing false positive results.
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Multiple markers are replaced by the single locus method with the numerous locus method. These changes will make the identification of covariant easier.
Conclusion:
Gamma hydroxybutyric acidemia is a comparatively rare disorder. The symptoms associated with these disorders irritate the child and hamper the child's growth. Hence, the goal of the doctors and parents should be focused on relieving the child's symptoms. Several research works are being done that aim at improving the treatment approaches. Gene therapy is the latest treatment protocol that is being extensively studied. Gene therapy targets faulty genes and enhances their function to cure the disorder.
