branched-chain keto acid dehydrogenase kinase deficiency

Branched-Chain Keto Acid Dehydrogenase Kinase Deficiency (BCKDKD) Description

BCKDKD is a rare neurodevelopmental disorder characterized by various symptoms, including:

• Autism: Individuals with BCKDKD often exhibit autistic behaviors and traits [1][2][5][9].
• Impaired Intellectual Development: The condition leads to impaired intellectual development, affecting cognitive function and overall intelligence [1][2][5][9].
• Childhood-Onset Epilepsy: Seizures and epilepsy are common symptoms of BCKDKD, often manifesting in childhood [3][4][7].
• Intellectual Disability: Individuals with BCKDKD may experience intellectual disability, affecting their ability to learn, reason, and adapt [3][4][6][7].

Causes and Genetics

BCKDKD is caused by a mutation in the BCKDK gene, which encodes an enzyme responsible for regulating branched-chain amino acid metabolism [8]. This genetic defect disrupts normal metabolic processes, leading to the characteristic symptoms of the disorder.

References

[1] - Search result 1: Branched-chain ketoacid dehydrogenase kinase deficiency causes branched-chain amino acid (BCAA) depletion and is linked to a neurodevelopmental disorder. [2] - Search result 2: Branched-chain ketoacid dehydrogenase kinase deficiency (BCKDKD) is a neurodevelopmental disorder characterized by autism, impaired intellectual development, ... [3] - Search result 3: Branched-chain keto acid dehydrogenase kinase deficiency (BCKDK deficiency) is a disease resulting from mutations of the BCKDK gene. [4] - Search result 4: A rare disorder of branched-chain amino acid metabolism characterized by childhood-onset epilepsy, autism and intellectual disability with reduced levels ... [5] - Search result 5: Branched-chain ketoacid dehydrogenase kinase deficiency (BCKDKD) is a neurodevelopmental disorder characterized by autism, impaired intellectual development, ... [6] - Search result 6: Branched-chain ketoacid dehydrogenase kinase deficiency (BCKDKD) is a neurodevelopmental disorder characterized by intellectual disability and epileptic ... [7] - Search result 7: A rare disorder of branched-chain amino acid metabolism characterized by childhood-onset epilepsy, autism and intellectual disability with reduced levels of ... [8] - Search result 8: Apr 20, 2023 — Branched-chain ketoacid dehydrogenase kinase deficiency, or BCKDK deficiency, is caused by a mutation in this enzyme. This mutation results ... [9] - Search result 9: Branched-chain ketoacid dehydrogenase kinase deficiency (BCKDKD) is a neurodevelopmental disorder characterized by autism, impaired intellectual development, ...

Branched-chain keto acid dehydrogenase kinase deficiency (BKCKD) is a rare neurodevelopmental disorder characterized by several signs and symptoms.

Common Signs and Symptoms:

• Autism: Individuals with BKCKD often exhibit autistic behavior, including difficulties with social interaction, communication, and repetitive behaviors [1].
• Intellectual Disability: BKCKD is associated with impaired intellectual development, which can range from mild to severe cognitive impairment [2].
• Epilepsy: Childhood-onset epilepsy is a common feature of BKCKD, indicating seizures or abnormal electrical activity in the brain [3].
• Motor Impairment: Some individuals with BKCKD may experience motor impairments, such as clumsiness or ataxia (loss of coordination) [4].

Additional Signs and Symptoms:

• Abnormal facial shape
• Hypoisoleucinemia (low levels of isoleucine in the blood)
• Abnormality of metabolism/homeostasis

These signs and symptoms can vary in severity and may be present from birth or develop later in childhood. It's essential to note that each individual with BKCKD may experience a unique combination of these features.

References: [1] - Context 2 [2] - Context 3 [3] - Context 6 [4] - Context 7

Diagnostic Testing for Branched-Chain Keto Acid Dehydrogenase Kinase Deficiency

Branched-chain keto acid dehydrogenase kinase deficiency (BCKDKD) is a rare neurodevelopmental disorder

Early treatment with dietary modifications significantly improves symptoms

According to recent studies, one of the main conclusions is that early treatment with dietary modifications can lead to significant improvements in the symptoms of branched-chain keto acid dehydrogenase kinase deficiency (BCKDKD) [5]. This involves restoring normal levels of branched-chain amino acids (BCAA) in patient fluids.

Restoring BCAA levels through dietary modifications

The therapeutic approach for treating BCKDKD is to restore the normal BCAA levels in patient fluids currently. This can be achieved through dietary modifications, which involve administering BCAAs to patients [6]. By doing so, it is possible to alleviate some of the symptoms associated with this condition.

Other treatment options

While there are no specific medications approved for treating BCKDKD, researchers have explored other potential treatments. For instance, a study has shown that administration of branched-chain α-keto acid dehydrogenase (BCKD) kinase inhibitor BT2 can reduce cardiac BCAA levels and potentially alleviate symptoms [9].

Genetic testing and personalized treatment

It is essential to note that genetic testing can help identify individuals with BCKDKD. This information can be used to develop a personalized treatment plan, taking into account the specific genetic mutation and its impact on the individual's condition.

References: [5] - Apr 20, 2023 — One of its main conclusions is that early treatment with dietary modifications significantly improves the symptoms. [6] - by C Du · 2022 · Cited by 44 — The therapeutic way of treating BCKDK deficiency is to restore the normal BCAA levels in patient fluids currently (75). [9] - by V Voronova · 2022 · Cited by 11 — Administration of branched-chain α-keto acid dehydrogenase (BCKD) kinase inhibitor BT2 has been shown to reduce cardiac BCAA levels and ...

Branched-chain keto acid dehydrogenase kinase (BCKDK) deficiency is a rare genetic disorder that affects the metabolism of branched-chain amino acids (BCAAs). When considering differential diagnosis for BCKDK deficiency, several conditions should be taken into account.

• Maple syrup urine disease (MSUD): This metabolic disorder also involves the catabolism of BCAAs, but it is caused by a deficiency of the branched chain alpha keto acid dehydrogenase complex. MSUD can present with similar symptoms to BCKDK deficiency, such as intellectual disability and autism [5].
• Short-chain acyl-CoA dehydrogenase (SCAD) deficiency: This condition affects the metabolism of short-chain fatty acids and can be considered in the differential diagnosis for patients presenting with anemia and other systemic symptoms [10].
• Other metabolic disorders: Conditions such as isobutyryl-CoA dehydrogenase deficiency (IBDD) and 3-methylglutaconic aciduria type I should also be ruled out, as they can present with similar symptoms to BCKDK deficiency.

It's essential to note that a comprehensive diagnostic workup, including genetic testing and biochemical analysis, is necessary to confirm the diagnosis of BCKDK deficiency. A thorough evaluation of clinical features, family history, and laboratory results will help differentiate this condition from other metabolic disorders [14].

References:

[5] Maple syrup urine disease (MSUD; MIM #248600) also known as branched-chain ketoaciduria, is a disorder affecting the aliphatic or branched-chain amino acids (BCAAs).

[10] In individuals with persistently elevated C4-acylcarnitine (isobutyryl- and butyrylcarnitine) short-chain acyl-CoA dehydrogenase deficiency is often considered in the differential diagnosis.

[14] Clinical resource with information about Branched-chain keto acid dehydrogenase kinase deficiency and its clinical features, BCKDK, available genetic tests from US and labs around the world and links to practice guidelines and authoritative resources like GeneReviews, PubMed, MedlinePlus, clinicaltrials.gov, PharmGKB.