Introduction
Alfa-methyl acetoacetic aciduria is the other name for β-ketothiolase deficiency. It has an autosomal recessive inheritance pattern, meaning the risk of disease inheritance by a child from parents is 25 percent. It is a rare disorder; medical literature states that approximately one per million or fewer newborns have a β-ketothiolase deficiency. It is an important enzyme and is responsible for the metabolism of ketone bodies produced from the breakdown of fats it is also responsible for the breakdown of a protein named isoleucine. Isoleucine is accountable for body growth, boosting body immunity, and glucose transportation required to produce energy. Therefore, individuals suffering from β-ketothiolase deficiency tend to have weakened immunity, delayed healing, and growth retardation. Most of them are lethargic.
How Does β-Ketothiolase Deficiency Occur?
It is a rare genetic condition and is caused due to genetic errors. The structural changes in the genes (mutation) and the DNA (deoxyribonucleic acid) sequence alterations are the genetic errors that cause this deficiency. Researchers have identified around a hundred mutations in the gene while genetic mapping is related to a child's β-ketothiolase deficiency. Medical research papers mention mutations in the ACAT1 gene (a gene that encodes for acetyl-CoA acetyltransferase) responsible for the deficiency of β-ketothiolase. Acetyl-CoA acetyltransferase is an enzyme responsible for energy production in the mitochondria. The mutations lead to a shortage of acetyl-CoA acetyltransferase enzyme. Thus, the body's metabolism of fats and proteins gets disturbed, resulting in increased ketone body production leading to toxin deposition in the blood, and the nature of the blood turns acidic. Further, it can also lead to neurological damage in the child.
What Is the Process by Which the Child Inherits β-Ketothiolase Deficiency?
β-ketothiolase deficiency is a rare disorder inherited genetically, and an autosomal recessive pattern is responsible for a child getting this disorder from parents. Autosomal recessive means both parents, father, and mother, carry one copy of the defective gene responsible for β-ketothiolase deficiency, but the parents do not show any signs and symptoms as the defective gene expressed by the parents, in this case, is recessive. So, in such cases, there is a one-fourth probability of their child suffering from this disease and expressing the disorder's symptoms. Genetic mapping can be done to identify the presence of the defective gene.
What Are the Signs and Symptoms Noted in a Child Having β-Ketothiolase Deficiency?
A child suffering from this disorder is mainly diagnosed between five months to two years.
They generally show no symptoms at the time of birth and appear normal. The first sign in these children is a ketoacidosis crisis (it is a life-threatening situation in which fat breakdown increases, leading to increased ketone formation and, in turn, the blood pH turns acidic). This state is aggravated when the child is exposed to increased stress, increased protein intake, or if the child has skipped meals for a very long time and is suffering from some infectious disease. Due to increased ketone levels, parents sometimes notice a fruity odor on their child's breath. Episodes of ketoacidosis crisis decrease as the age of the child advances.
Following are a few signs that parents should note in their child and seek medical advice if these signs are long-term:
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The child is very lethargic and sleeps for a longer duration than normal.
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Irritated and tired, not willing to play even after getting an ample amount of rest.
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Frequently complains of nausea and vomiting.
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A continuous low-grade fever is present.
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The child is not ready to eat, and the appetite keeps decreasing.
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The child suffers from diarrhea frequently.
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Breathing issues like difficulty in breathing and restlessness.
As early in life, β-ketothiolase deficiency gets diagnosed in a child, the management is easy, leading to reduced suffering in the child.
How Is β-Ketothiolase Deficiency Diagnosed in a Child?
β-ketothiolase deficiency can be diagnosed prenatally as well as during the infantile stage.
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For prenatal diagnosis, the sample is collected using molecular methods 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. Genetic mapping provides the location of the defective gene in the chromosome, and these locations can then be targeted using the gene therapy protocols for the treatment process.
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Medical specialists prescribe various biochemical laboratory tests for diagnosing β-ketothiolase deficiency.
Following are the few tests that are commonly prescribed:
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Urine analysis identifies the markers (enzymes responsible for fat and protein breakdown) and also notes the quantity of these markers.
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Fibroblast enzyme assay is a confirmatory test in diagnosing cases with β-ketothiolase deficiency.
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Computed tomography (CT scans) and magnetic resonance imaging (MRI) are done to check for the presence of any brain lesions or any other systemic causes responsible for the disorder.
Newborn screening programs are organized in various countries for early diagnosis of rare genetic disorders. This program collects samples from the infant child and is sent for genetic analysis. The sample is mostly collected by the method of blood spot collection. In this method, a small prick is made on the fingers of the child whose genetic assessment has to be done, and then the blood sample is collected from the prick on the fingers and is used for genetic analysis. These programs help in the mass screening of various rare genetic disorders. Prevalence and incidences of such rare diseases affecting the human population are recorded. It also guides genetic researchers in planning genetic therapy for rare genetic disorders.
What Are the Treatment Protocols for β-Ketothiolase Deficiency?
Ketoacidosis crisis is the most commonly noted condition in the child suffering from β-ketothiolase deficiency should be treated on time as it is a life-threatening situation. Glucose and electrolytes should be maintained through intravenous injections. Many researchers have proved Carnitine supplementation helpful in these conditions. Supported breathing through mechanical ventilation is prescribed for children having severe breathing disabilities. Apart from this diet intake of the child should be monitored. Prolonged fasting should be avoided, and the diet should not be rich in fats and protein.
Conclusion:
β-ketothiolase deficiency is a genetically inherited disease resulting in decreased body ability to metabolize ketone. The prognosis of children suffering from this disorder is considered to be good. Various studies are developing targeting genetic therapies for treating this disorder.
