Introduction
Medium/short-chain L-3-hydroxyacyl-CoA dehydrogenase (M/SCHAD) deficiency hinders the body's ability to produce adequate energy during periods of stress, illness, and fasting. When the body depletes its glucose reserves, it must resort to breaking down fats in a four-step process called beta-oxidation, which occurs in the mitochondria - the "powerhouses of the cell" - present in every cell in the body. M/SCHAD, a protein family member, catalyzes the third step in this process. Additionally, it has a distinct function within the mitochondria that regulates insulin secretion. In the absence of M/SCHAD, excess insulin is released into the bloodstream, resulting in low blood sugar levels. The loss of normal insulin regulation is the most perilous aspect of this deficiency.
What Is the Cause of M/SCHAD?
Enzymes play a crucial role in breaking down the food we consume, and specific enzymes are responsible for breaking down fats into their building blocks, known as fatty acids. These fatty acids differ in length and are categorized as short, medium, long, or very long. Each length of fatty acid requires a distinct enzyme to break it down. One such enzyme is the 3-hydroxyacyl-CoA dehydrogenase, which breaks down medium and short-chain fatty acids to produce energy. In the case of medium/short-chain L-3-hydroxyacyl-CoA dehydrogenase deficiency (M/SCHAD), this enzyme does not function correctly, leading to a shortage of energy production from the breakdown of medium and short-chain fatty acids.
Fatty acids are vital energy sources for the body, particularly the heart, when blood sugar levels are low, such as in between meals. The inability to break down these fatty acids can cause harmful substances to accumulate in the body, leading to various health issues.
M/SCHAD is a genetic disorder that follows an autosomal recessive inheritance pattern. This implies that a child must inherit two copies of the non-functioning gene, one from each parent, to develop the condition. Even though the parents of an affected child possess a single copy of the faulty gene, they generally do not exhibit any symptoms associated with the condition. If both parents are carriers of the non-functioning gene, they may have more than one child with the condition.
What Are the Symptoms?
Common indications of this disorder in fatty acid oxidation are:
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Profound drowsiness.
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Irritation.
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Decreased appetite.
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Alterations in mood.
Inadequate treatment may lead to the development of additional symptoms, such as:
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Elevated body temperature.
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Nausea and vomiting.
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Hypoglycemia (low blood sugar).
Studies on fatty acid oxidation have revealed that if left untreated, hypoglycemia can escalate and result in seizures and coma. Moreover, infants affected by M/SCHAD deficiency may develop liver disease. These symptoms typically manifest when the child experiences an illness for the first time and disrupts their regular eating habits. In such cases, infants with M/SCHAD deficiency do not have enough glucose in their bloodstream to produce energy when faced with minor stressors such as an ear infection or diarrhea. Their blood sugar levels are further depleted due to excessive insulin secretion, and their inability to utilize fat as a source of energy gives rise to the aforementioned symptoms.
How to Diagnose It?
The diagnosis of medium/short-chain L-3-hydroxyacyl-CoA dehydrogenase deficiency (M/SCHAD) usually involves a combination of clinical presentation, laboratory tests, and genetic testing. The symptoms of M/SCHAD can be nonspecific and may overlap with other conditions, making it challenging to diagnose the disorder based on clinical symptoms alone.
Laboratory testing for M/SCHAD includes blood tests to measure levels of glucose, insulin, and free fatty acids. Additionally, organic acid analysis in urine samples can provide evidence of incomplete breakdown of fatty acids.
Genetic testing can confirm a diagnosis of M/SCHAD by identifying mutations in the HADH gene, which is responsible for producing the enzyme that breaks down medium and short-chain fatty acids.
In some cases, newborn screening may detect M/SCHAD early on, allowing for prompt intervention and management. Screening methods typically involve the measurement of acylcarnitine levels in dried blood spots collected from newborns. Abnormal acylcarnitine levels may indicate the presence of a fatty acid oxidation disorder, including M/SCHAD.
How to Treat It?
The treatment of medium/short-chain L-3-hydroxyacyl-CoA dehydrogenase deficiency (M/SCHAD) involves a combination of approaches to manage symptoms and prevent complications. The main goal of treatment is to ensure that the body has adequate energy to function correctly.
The primary treatment for M/SCHAD involves a carefully controlled diet and close monitoring of blood glucose levels. Infants with M/SCHAD typically require frequent feedings to maintain their blood sugar levels and prevent symptoms of low blood sugar. Some infants with severe M/SCHAD may require a feeding tube to ensure adequate nutrition.
A specialized medical formula may be prescribed to provide medium-chain triglycerides (MCTs), which can be more easily broken down for energy than other types of fats. MCTs are also found in foods such as coconut oil and palm kernel oil and may be included in the diet as tolerated.
During periods of illness or fasting, additional glucose supplementation may be required to prevent hypoglycemia. In severe cases of M/SCHAD, hospitalization and intravenous glucose may be necessary.
It is essential to promptly manage any underlying health conditions that may trigger symptoms, such as infections or fever. Regular check-ups with a healthcare provider, including blood tests and urine analysis, may also be necessary to monitor treatment effectiveness and identify potential complications.
Carnitine supplements might be prescribed in certain instances to facilitate the transportation of fatty acids into the mitochondria, thereby supporting energy production. However, this is not typically recommended for M/SCHAD as the condition involves the production of an enzyme rather than a transport problem.
M/SCHAD is a lifelong condition that requires ongoing management. With proper treatment, individuals with M/SCHAD can live healthy and fulfilling lives. Working closely with the doctor and a registered dietitian is important to develop a comprehensive treatment plan tailored to the individual's needs.
Conclusion
Medium/short-chain L-3-hydroxyacyl-CoA dehydrogenase (M/SCHAD) deficiency is a genetic disorder that limits the body's ability to produce energy from medium and short-chain fatty acids, leading to low blood sugar levels and potentially life-threatening symptoms. Early diagnosis and proper management of this disorder through a controlled diet, regular glucose monitoring, and medical intervention during periods of illness or fasting can improve outcomes and prevent complications.
