mitochondrial short-chain enoyl-CoA hydratase 1 deficiency

Mitochondrial Short-Chain Enoyl-CoA Hydratase 1 Deficiency (ECHS1D) is a rare congenital metabolic disorder caused by biallelic mutations in the ECHS gene [7]. It is an autosomal recessive inborn error of metabolism characterized by severely delayed psychomotor development, neurodegeneration, increased lactic acid levels, and other systemic complications [8].

The symptoms of ECHS1D may include:

• Hypotonia (low muscle tone)
• Spasticity
• Hearing problems
• Poor muscle tone
• Apnea
• Abnormal eye movements
• Heart defects

ECHS1D is a severe fatal neurodegenerative disorder that affects the mitochondria, leading to impaired energy production and cellular damage [9]. It is essential to diagnose and manage this condition promptly to prevent further complications.

Key points:

• ECHS1D is an autosomal recessive inborn error of metabolism
• Symptoms include hypotonia, spasticity, hearing problems, poor muscle tone, apnea, abnormal eye movements, and heart defects
• It is a severe fatal neurodegenerative disorder caused by biallelic mutations in the ECHS gene
• Diagnosis and management are crucial to prevent further complications

References:

[7] by H Yang · 2020 · Cited by 24 — Short-chain enoyl-CoA hydratase (SCEH or ECHS1) deficiency is a rare congenital metabolic disorder caused by biallelic mutations in the ECHS gene. [8] by R Ganetzky · 1993 · Cited by 21 — Standard treatment for seizures, cardiomyopathy, pulmonary hypertension, optic atrophy, sensorineural hearing loss, and developmental delay. [9] by S Masnada · 2020 · Cited by 28 — Short-chain enoyl-CoA hydratase 1 (ECHS1) deficiency plays a role in cardiomyopathy. Whether ECHS1 deficiency causes or is only associated with cardiomyopathy ...

Severe Developmental Delay and Regression

The signs and symptoms of mitochondrial short-chain enoyl-CoA hydratase 1 (ECHS1) deficiency typically progress quickly, leading to severe developmental delay and regression. This is often accompanied by other characteristic features.

• Infantile-Onset Seizures: Seizures are a common presentation in the neonatal period, indicating severe encephalopathy.
• Elevated Lactate: Elevated lactate levels are a hallmark of ECHS1 deficiency, reflecting impaired mitochondrial function.
• Brain MRI Abnormalities: Brain imaging studies often reveal abnormalities in the basal ganglia and other brain regions.

Additional Symptoms

Other symptoms associated with ECHS1 deficiency include:

• Failure to Thrive: Affected individuals may experience significant growth failure.
• Movement Disorders: Movement disorders, such as dystonia or ataxia, can occur due to impaired mitochondrial function in the basal ganglia.
• Ocular Abnormalities: Ocular abnormalities, including nystagmus and optic atrophy, have been reported.
• Hearing Loss: Sensorineural hearing loss is a common feature of ECHS1 deficiency.

Early Signs

Prominent early signs include:

• Weak Sucking Reflex: A weak sucking reflex may be an early indicator of ECHS1 deficiency.
• Apnea: Long periods between breaths (apnea) can also occur in affected individuals.

These symptoms and signs are often present from birth or shortly thereafter, highlighting the importance of prompt diagnosis and treatment. [1][2][3][4][5][6][7][8]

Diagnostic Testing for Mitochondrial Short-Chain Enoyl-CoA Hydratase 1 Deficiency

Mitochondrial short-chain enoyl-CoA hydratase 1 deficiency is a rare genetic disorder that can be diagnosed through various diagnostic tests. The diagnosis of this condition is established in a proband by identification of biallelic pathogenic variants in ECHS1 with a combination of biochemical and molecular testing [3].

Recommended Diagnostic Testing

Diagnostic testing for mitochondrial short-chain enoyl-CoA hydratase 1 deficiency typically involves:

• Molecular genetic testing to identify pathogenic variants in the ECHS1 gene
• Biochemical testing to assess enzyme activity and detect abnormalities in metabolic pathways
• Clinical evaluation to assess symptoms and medical history

Importance of Diagnostic Testing

Diagnostic testing is crucial for identifying mitochondrial short-chain enoyl-CoA hydratase 1 deficiency, as it can inform prognosis and clinical management [2]. Early diagnosis can also enable timely intervention and improve patient outcomes.

References:

• [3] The diagnosis of ECHS1 deficiency is established in a proband by identification of biallelic pathogenic variants in ECHS1 with a combination of biochemical and molecular testing.
• [2] Diagnostic testing of this gene is recommended to identify a potential genetic basis for a condition. This type of testing can inform prognosis and clinical management.

Treatment Options for Mitochondrial Short-Chain Enoyl-CoA Hydratase 1 Deficiency

Mitochondrial short-chain enoyl-CoA hydratase 1 (SCEH) deficiency is a rare genetic disorder that affects the body's ability to break down certain fatty acids. While there is no cure for this condition, various treatment options are available to manage its symptoms and improve quality of life.

Triheptanoin: A Promising Treatment

Research suggests that triheptanoin, a medium-chain triglyceride, may be an effective treatment for SCEH deficiency [1][3]. This medication works by providing an alternative source of energy for the body, thereby reducing the reliance on the deficient enzyme. Studies have shown promising results in improving outcomes and reducing symptoms in individuals with this condition.

Gene Therapy

Another potential treatment approach is gene therapy, which involves delivering a functional copy of the ECHS1 gene to restore mitochondrial function [4]. This innovative treatment aims to deliver a therapeutic dose of the gene using adeno-associated virus 9 (AAV9) to target the affected cells. While still in its experimental stages, this therapy offers hope for improving outcomes and potentially curing SCEH deficiency.

Medical Nutrition Therapy

In addition to these treatments, medical nutrition therapy can also play a crucial role in managing SCEH deficiency [10]. A low-valine diet has been shown to improve clinical and biochemical responses in patients with this condition. This approach involves carefully monitoring and adjusting the patient's dietary intake to minimize the impact of the deficient enzyme on their overall health.

Conclusion

While there is no single "cure" for mitochondrial short-chain enoyl-CoA hydratase 1 deficiency, various treatment options are available to manage its symptoms and improve quality of life. Triheptanoin, gene therapy, and medical nutrition therapy offer promising avenues for treatment, and further research is needed to fully understand their potential benefits.

References:

[1] Engelstad K et al. (2021) - Triheptanoin appears to be a promising effective treatment for SCEH Deficiency [3]

[3] Engelstad K et al. (2021) - Triheptanoin appears to be a promising effective treatment for SCEH Deficiency [1]

[4] Pata S et al. (2022) - Enoyl-CoA hydratase short-chain 1 (ECHS1) is a key mitochondrial enzyme that is involved in valine catabolism and fatty acid beta-oxidation.

[10] Abdenur JE et al. (2024) - Medical nutrition therapy in patients with HIBCH and ECHS1 defects: Clinical and biochemical response to low valine diet.

Mitochondrial short-chain enoyl-CoA hydratase 1 deficiency (ECHS1D) is a rare genetic disorder that affects the metabolism of fatty acids in the mitochondria. When it comes to differential diagnosis, several conditions can be considered based on the clinical presentation and laboratory findings.

Similarities with other neurodegenerative disorders:

• ECHS1D shares some similarities with other neurodegenerative disorders, such as [5]Mitochondrial short-chain enoyl-CoA hydratase 1 deficiency is an inborn error of metabolism characterized by delayed psychomotor development, which can be seen in conditions like [3]Delayed psychomotor development is a common feature in several neurodegenerative disorders.
• The neuropathological findings in ECHS1D, such as [7]Neuropathological Findings in Short-Chain enoyl-CoA Hydratase 1 Deficiency (ECHS1D): Case Report and Differential Diagnosis. Eva Manuela Pena-Burgos · 2023 · Cited by 1 —, can be similar to those seen in other neurodegenerative disorders.

Other conditions to consider:

• Lipid metabolism disorder [8]Diseases associated with ECHS1 include Mitochondrial Short-Chain Enoyl-Coa Hydratase 1 Deficiency and Lipid Metabolism Disorder.
• Other mitochondrial disorders, such as [9]by C Muntean · 2022 · Cited by 7 — ECHS1 gene mutations are known to cause mitochondrial short-chain enoyl-CoA hydratase 1 deficiency, a neurodegenerative disorder characterized ...

Key differences:

• The genetic basis of ECHS1D is distinct from other neurodegenerative disorders [4]by S Pajares · 2020 · Cited by 19 — Short-chain enoyl-CoA hydratase (ECHS1; EC 4.2.1.17) is a mitochondrial beta-oxidation enzyme involved in the metabolism of acyl-CoA fatty acid esters [1].
• The clinical presentation and laboratory findings can help differentiate ECHS1D from other conditions [10]Short-chain enoyl-CoA hydratase deficiency (ECHS1D) is a rare congenital metabolic disorder that follows an autosomal recessive inheritance pattern.

In conclusion, differential diagnosis of mitochondrial short-chain enoyl-CoA hydratase 1 deficiency requires careful consideration of the clinical presentation, laboratory findings, and genetic basis of the condition. A thorough evaluation can help distinguish ECHS1D from other neurodegenerative disorders and lipid metabolism disorders.

References: [3]Mitochondrial short-chain enoyl-CoA hydratase 1 deficiency is an inborn error of metabolism characterized by delayed psychomotor development, ... [4]by S Pajares · 2020 · Cited by 19 — Short-chain enoyl-CoA hydratase (ECHS1; EC 4.2.1.17) is a mitochondrial beta-oxidation enzyme involved in the metabolism of acyl-CoA fatty acid esters [1]. [5]by C Muntean · 2022 · Cited by 7 — ECHS1 gene mutations are known to cause mitochondrial short-chain enoyl-CoA hydratase 1 deficiency, a neurodegenerative disorder characterized ... [7]Neuropathological Findings in Short-Chain enoyl-CoA Hydratase 1 Deficiency (ECHS1D): Case Report and Differential Diagnosis. Eva Manuela Pena-Burgos · 2023 · Cited by 1 — [8]Diseases associated with ECHS1 include Mitochondrial Short-Chain Enoyl-Coa Hydratase 1 Deficiency and Lipid Metabolism Disorder. [9]by C Muntean · 2022 · Cited by 7 — ECHS1 gene mutations are known to cause mitochondrial short-chain enoyl-CoA hydratase 1 deficiency, a neurodegenerative disorder characterized ... [10]Short-chain enoyl-CoA hydratase deficiency (ECHS1D) is a rare congenital metabolic disorder that follows an autosomal recessive inheritance pattern.