beta-ketothiolase deficiency

Beta-ketothiolase deficiency is an inherited disorder that affects the body's ability to process a protein building block called isoleucine and ketones, which are molecules produced during the breakdown of fats.

Clinical Description

The condition typically presents in infancy or early childhood, with symptoms appearing between 5 months to 2 years of age. The onset of symptoms usually occurs in the form of a ketoacidotic crisis, most often accompanied by vomiting, lethargy, and other systemic disturbances [1][4].

Key Features

• Inherited disorder affecting isoleucine metabolism
• Impaired ability to process ketones
• Typical presentation between 5 months to 2 years of age
• Ketoacidotic crises with symptoms such as vomiting, lethargy, and systemic disturbances

Symptoms

People with beta-ketothiolase deficiency may experience a range of symptoms, including:

• Nervousness, shakiness, weakness, or sweating [8]
• Headache, blurred vision, and hunger
• If left untreated, the condition can lead to more severe complications.

Genetic Aspect

Beta-ketothiolase deficiency is an autosomal recessive inherited disorder, meaning that a person must inherit two copies of the mutated gene (one from each parent) to develop the condition [7].

References

[1] Beta-ketothiolase deficiency is an inherited disorder in which the body cannot effectively process a protein building block called isoleucine. This disorder also impairs the body's ability to process ketones, which are molecules produced during the breakdown of fats.

[2] Clinical description T2 deficiency is clinically characterized by intermittent ketoacidotic crises with however no clinical symptoms between these episodes.

[3] Beta-ketothiolase deficiency is an inherited (genetic) condition that prevents the body from breaking down certain proteins and fats.

[4] Children often appear normal at birth with disease presentation typically between the ages of 5 months to 2 years; however, presentation may occur anywhere between birth and childhood.

[5] Beta-ketothiolase deficiency (BKT) is an inherited condition in which the body is unable to break down certain proteins. People with the condition are also impaired due to the body's inability to process ketones.

[7] Beta-ketothiolase deficiency is an autosomal recessive inherited disorder in which the body is impaired due to the body's inability to process ketones.

[8] It may cause a person to feel nervous, shaky, weak, or sweaty. It may also cause headache, blurred vision, and hunger. If left untreated, it can cause more severe complications.

[13] Beta-ketothiolase deficiency is a rare, autosomal recessive metabolic disorder in which the body cannot properly process the amino acid isoleucine or the products of lipid breakdown.

Signs and Symptoms of Beta-Ketothiolase Deficiency

Beta-ketothiolase deficiency, also known as beta-ketothiolase deficiency disorder or BKT deficiency, is a rare inherited metabolic disorder that affects the body's ability to break down certain proteins and fats. The signs and symptoms of this condition typically appear in early childhood, between 6 months and 24 months of age.

Common Signs and Symptoms:

• Vomiting
• Dehydration
• Difficulty breathing
• Extreme tiredness (lethargy)
• Occasionally, seizures or convulsions

These episodes, known as ketoacidotic attacks, can sometimes lead to coma if not treated promptly. The frequency and severity of these attacks can vary depending on the individual case.

Other Possible Symptoms:

• Poor appetite
• Diarrhea
• Fever
• Irritable mood and behavior changes
• Sleeping longer or more often

In some cases, people with beta-ketothiolase deficiency may not show any signs or symptoms at all. However, when symptoms do occur, they can be triggered by factors such as illness, fasting, or a high-protein meal.

Important Note:

Beta-ketothiolase deficiency is an autosomal recessive inherited disorder, meaning that both parents must be carriers of the mutated gene for their child to develop the condition. If you suspect that your child may have beta-ketothiolase deficiency, it's essential to consult with a healthcare professional for proper diagnosis and treatment.

References:

• [1] The signs and symptoms of beta-ketothiolase deficiency typically appear between the ages of 6 months and 24 months. Affected children experience episodes of vomiting, dehydration, difficulty breathing, extreme tiredness (lethargy), and, occasionally, seizures.
• [2] Signs of beta-ketothiolase deficiency usually start around 1 year of age, though this can range from 6 months to 2 years.
• [3] The signs and symptoms of beta-ketothiolase deficiency include vomiting, dehydration, trouble breathing, extreme tiredness, and occasionally convulsions.
• [4] Beta ketothiolase deficiency is inherited in an autosomal recessive fashion and is caused by pathogenic variants in the ACAT1 gene.

Beta-ketothiolase deficiency (BKT) can be diagnosed through various diagnostic tests, which are crucial for confirming the condition and ruling out other potential causes.

Diagnostic Testing

According to search result [2], diagnostic testing may include:

• Urine organic acid analysis
• Plasma acylcarnitine analysis
• ACAT1 gene sequencing
• Enzyme analysis in fibroblasts

These tests can help identify the presence of beta-ketothiolase deficiency and rule out other conditions. It's worth noting that in milder cases, the urine organic acid analysis and acylcarnitine profile may be normal unless an isoleucine challenge is given [2].

Confirmatory Tests

Search result [3] mentions that diagnosis can be confirmed by:

• Cultured fibroblast enzyme assays (reduced potassium-dependent acetoacetyl-CoA thiolase activity)
• Molecular genetic testing

These confirmatory tests are essential for establishing a definitive diagnosis of beta-ketothiolase deficiency.

Other Diagnostic Tests

Search result [8] suggests that routine laboratory tests, such as electrolytes, blood gas, glucose, ammonia, and urinary organic acid analysis or blood acyl-carnitine analysis, can provide diagnostic clues. Additionally, search result [12] mentions the importance of collecting critical samples (blood, serum, and urine) before treatment is started.

Carrier Testing

Search result [9] notes that brothers and sisters of a child with BKT can be tested using blood, urine, or skin samples to determine if they are carriers of the condition. Carrier testing can help identify individuals who may not have symptoms but can pass the mutated gene to their offspring.

In summary, diagnostic tests for beta-ketothiolase deficiency include urine organic acid analysis, plasma acylcarnitine analysis, ACAT1 gene sequencing, enzyme analysis in fibroblasts, cultured fibroblast enzyme assays, molecular genetic testing, and carrier testing. These tests are essential for confirming the diagnosis and ruling out other potential causes.

References:

[2] Diagnostic testing may include urine organic acid analysis, plasma acylcarnitine analysis, ACAT1 gene sequencing, and enzyme analysis in fibroblasts. [3] Diagnosis can be confirmed by cultured fibroblast enzyme assays (reduced potassium-dependent acetoacetyl-CoA thiolase activity) and molecular genetic testing. [8] Routine laboratory tests, such as electrolytes, blood gas, glucose, ammonia, and urinary organic acid analysis or blood acyl-carnitine analysis, can provide diagnostic clues. [12] Critical samples (blood, serum, and urine) should be collected before treatment is started.

Beta-ketothiolase deficiency is a rare genetic disorder that affects the body's ability to break down certain proteins and produce ketone bodies, an important energy source during fasting or illness.

Treatment Overview

While there is no cure for beta-ketothiolase deficiency, treatment involves managing the condition through dietary modifications and supplements. The primary goal of treatment is to prevent complications associated with the disorder.

• Dietary Management: A special diet that is low in proteins and high in fats can help manage the condition. This diet may need to be adjusted based on individual needs.
• L-Carnitine Supplementation: L-carnitine supplements have been shown to be beneficial in managing beta-ketothiolase deficiency, particularly in cases with a low carnitine level [15].
• Carnitine Therapy: Carnitine therapy can be considered as part of the treatment plan [8].

Other Considerations

It's essential to note that people with beta-ketothiolase deficiency require specialized treatment through a specialty clinic with experience in treating this disorder. Treatment is typically dietary management, including careful monitoring of protein and carbohydrate intake, and may involve additional medical care during times of illness.

In some cases, children may show signs of the condition even with treatment, but these signs usually decrease with age [7]. However, it's crucial to work closely with a healthcare provider to develop an individualized treatment plan that meets specific needs.

References

• [15] M Alijanpour · 2019 · Cited by 6 — In addition to frequent feeding, l-carnitine supplementation (50 mg/kg/day) was started. As shown in Table 1, after carnitine supplementation, she had three ...
• [8] Clinical symptoms and treatment are typical for an organic acidemia. Carnitine therapy can be considered.
• [7] There are some cases where children show signs of beta-ketothiolase deficiency (BKT) even with treatment. However, these signs usually decrease with age. If ...

Differential Diagnosis of Beta-Ketothiolase Deficiency

Beta-ketothiolase deficiency, also known as mitochondrial acetoacetyl-CoA thiolase (T2) deficiency, is a rare genetic disorder that affects the body's ability to break down certain amino acids and fatty acids. The differential diagnosis of this condition involves identifying other possible causes of similar symptoms.

Other Organic Acidurias

• 3-methylcrotonyl-CoA carboxylase (3MCC) deficiency: This is a condition where the body is unable to properly metabolize certain amino acids, leading to the accumulation of toxic compounds in the urine and blood. [6]
• 2-methyl-3-hydroxybutyryl-CoA dehydrogenase deficiency: This is another rare genetic disorder that affects the metabolism of certain amino acids, leading to similar symptoms as beta-ketothiolase deficiency. [8]

Other Conditions

• Sepsis: A life-threatening condition caused by an overwhelming infection in the body.
• HSD10 disease: A rare genetic disorder that affects the metabolism of certain amino acids and fatty acids.
• Succinyl-CoA:3-ketoacid CoA transferase deficiency: A rare genetic disorder that affects the metabolism of certain amino acids and fatty acids.

Clinical Manifestations

The clinical manifestations of beta-ketothiolase deficiency can vary widely, but often include:

• Ketoacidotic attacks
• Vomiting and dehydration
• Lethargy and coma

These symptoms are similar to those seen in other organic acidurias and conditions that cause ketoacidosis in childhood.

References

• Abdelkreem et al. (2019) [3]
• Alijanpour et al. (2019) [4]
• Grünert et al. (2020) [5]

Note: The numbers in square brackets refer to the search results provided in the context, which were used to generate this answer.