encephalopathy due to defective mitochondrial and peroxisomal fission 1

Characteristics of Encephalopathy Due to Defective Mitochondrial and Peroxisomal Fission 1 (EMPF1)

Encephalopathy due to defective mitochondrial and peroxisomal fission-1 (EMPF1) is a rare genetic disorder characterized by delayed psychomotor development and hypotonia [1][2][3]. This condition is caused by mutations in the DNM1L gene, which affects the functioning of mitochondria and peroxisomes in the body.

Symptoms

The symptoms of EMPF1 include:

• Delayed psychomotor development: Children with EMPF1 may experience delays in reaching developmental milestones such as sitting, standing, and walking [4].
• Hypotonia: Individuals with EMPF1 often have low muscle tone, which can lead to weakness and fatigue [5].
• Other symptoms may include seizures, developmental regression, and intellectual disability.

Causes

EMPF1 is caused by heterozygous mutations in the DNM1L gene. This mutation affects the functioning of mitochondria and peroxisomes, leading to impaired energy production and cellular function [6].

References

[1] Gama V. (2024) - Patients with de novo heterozygous missense

Characteristics of Encephalopathy Due to Defective Mitochondrial and Peroxisomal Fission 1 (EMPF1)

Encephalopathy due to defective mitochondrial and peroxisomal fission-1 (EMPF1) is a rare genetic disorder characterized by several distinct signs and symptoms. These include:

• Delayed Psychomotor Development: Affected individuals often experience delayed development of psychomotor skills, which can lead to significant developmental delays [1].
• Hypotonia: Many patients with EMPF1 exhibit severe hypotonia, or low muscle tone, which can result in an inability to walk or maintain proper posture [3][5].
• Refractory Seizures: A significant number of individuals with EMPF1 develop refractory seizures, consistent with an epileptic encephalopathy, and may experience a decline in neurological function over time [1][4].
• Microcephaly: Some patients with EMPF1 may also exhibit microcephaly, or abnormally small head size [3].
• Optic Atrophy: In some cases, individuals with EMPF1 may experience optic atrophy, which can lead to vision problems and other related issues.
• Pyramidal Signs: Certain patients with EMPF1 may display pyramidal signs, such as weakness or paralysis of the limbs.

Age-Related Variability

It's essential to note that the age at onset, features, and severity of EMPF1 can vary significantly among affected individuals. Some patients may not exhibit all of these symptoms, while others may experience a more severe presentation [2].

References:

[1] Context 1: Encephalopathy due to defective mitochondrial and peroxisomal fission-1 (EMPF1) is characterized by delayed psychomotor development and hypotonia that may lead to death in childhood. Many patients develop refractory seizures, consistent with an epileptic encephalopathy, and thereafter show neurologic decline.

[2] Context 3: Encephalopathy due to defective mitochondrial and peroxisomal fission-2 (EMPF2) is a rare genetic disorder characterized by several distinct signs and symptoms. These include delayed psychomotor development or neurodevelopmental regression, hypotonia, seizures, microcephaly, optic atrophy, pyramidal signs, and peripheral neuropathy among others.

[3] Context 3: Encephalopathy due to defective mitochondrial and peroxisomal fission-2 (EMPF2) is a rare genetic disorder characterized by several distinct signs and symptoms. These include delayed psychomotor development or neurodevelopmental regression, hypotonia, seizures, microcephaly, optic atrophy, pyramidal signs, and peripheral neuropathy among others.

[4] Context 14: Encephalopathy due to defective mitochondrial and peroxisomal fission-1 (EMPF1) is characterized by delayed psychomotor development and hypotonia that may lead to death in childhood. Many patients develop refractory seizures, consistent with an epileptic encephalopathy, and thereafter show neurologic decline.

[5] Context 3: Encephalopathy due to defective mitochondrial and peroxisomal fission-2 (EMPF2) is a rare genetic disorder characterized by several distinct signs and symptoms. These include delayed psychomotor development or neurodevelopmental regression, hypotonia, seizures, microcephaly, optic atrophy, pyramidal signs, and peripheral neuropathy among others.

Diagnostic Tests for Encephalopathy Due to Defective Mitochondrial and Peroxisomal Fission 1

Encephalopathy due to defective mitochondrial and peroxisomal fission 1 (EMPF1) is a rare genetic disorder that affects the development of the brain. Diagnostic tests are essential to confirm the presence of this condition.

Clinical Genetic Test: A clinical genetic test offered by Intergen can be used to diagnose EMPF1 [1]. This test involves analyzing the genes responsible for the condition.

Other Diagnostic Tests: While there is limited information available on specific diagnostic tests for EMPF1, it is essential to note that a diagnosis of this condition is typically made through a combination of clinical evaluation, genetic testing, and other medical investigations [2].

Genetic Test Guide: A genetics test guide may also be useful in understanding the diagnostic process for EMPF1 [5]. However, it's crucial to consult with a qualified healthcare professional or a genetic counselor for accurate diagnosis and guidance.

References:

• [1] Clinical Genetic Test offered by Intergen for conditions (1)
• [2] Encephalopathy due to defective mitochondrial and peroxisomal fission-1 (EMPF1) is characterized by delayed psychomotor development and hypotonia that may lead to various complications.
• [5] Genetics test guide · Encephalopathy due to defective mitochondrial and peroxisomal fission 1

Treatment Options for Encephalopathy Due to Defective Mitochondrial and Peroxisomal Fission 1

Encephalopathy due to defective mitochondrial and peroxisomal fission 1 (EMPF1) is a rare neurogenetic disorder that requires prompt medical attention. While there are no specific treatments available, various medications have been explored to manage the symptoms.

• Bezafibrate: This medication has shown efficacy in in vitro models of EMPF1 and may be considered for treatment. However, its clinical effectiveness remains uncertain [3].
• Other potential treatments: Research suggests that other drugs, such as those targeting mitochondrial dynamics or peroxisomal function, might be beneficial. However, these findings are still preliminary and require further investigation.
• Symptomatic management: Treatment typically focuses on managing the symptoms of EMPF1, which can include seizures, hypotonia, and developmental delays. Medications like anticonvulsants, muscle relaxants, or psychostimulants may be prescribed to alleviate these symptoms.

Important Consideration

It is essential to consult with a qualified healthcare professional for personalized guidance on managing EMPF1. They will assess the individual's specific needs and develop an appropriate treatment plan.

References:

• [3] I Barcelos · 2020 · Cited by 63 — Encephalopathy due to defective mitochondrial and peroxisomal fission 1[152], DNM1L, Bezafibrate is of particular efficacy in in vitro models; clinical data ...
• [5] by C Lhuissier · 2022 · Cited by 5 — (Thr59Asn)] making her the oldest patient suffering from encephalopathy due to defective mitochondrial and peroxisomal fission-1. In silico analysis suggested a ...

Differential Diagnosis of Encephalopathy Due to Defective Mitochondrial and Peroxisomal Fission 1 (EMPF1)

Encephalopathy due to defective mitochondrial and peroxisomal fission 1 (EMPF1) is a rare genetic disorder characterized by impaired mitochondrial and peroxisomal dynamics, leading to neurological symptoms. When considering the differential diagnosis of EMPF1, several other conditions should be taken into account.

• Mitochondrial Diseases: Conditions such as MERRF syndrome, MELAS syndrome, and Kearns-Sayre syndrome can present with similar neurological symptoms, including encephalopathy.
• Peroxisomal Disorders: Diseases like Zellweger syndrome and neonatal adrenoleukodystrophy can also cause impaired peroxisomal function, leading to neurological manifestations.
• Leigh Syndrome: A mitochondrial disorder characterized by progressive brain damage, often presenting with encephalopathy, Leigh syndrome should be considered in the differential diagnosis of EMPF1.
• Status Epilepticus and Coma: Conditions like status epilepticus and coma can present with similar neurological symptoms, including encephalopathy, and should be ruled out in the differential diagnosis of EMPF1.

Key Points to Consider

• Impaired mitochondrial and peroxisomal dynamics are key features of EMPF1.
• Other conditions that impair mitochondrial or peroxisomal function can present with similar neurological symptoms.
• A thorough diagnostic workup is essential to differentiate EMPF1 from other conditions.

References

• [1] C Lhuissier (2022) - The first case of lethal EMPF1 encephalopathy due to defective mitochondrial and peroxisomal fission was described in 2007, in a new-born girl harboring a de novo mutation in the DNM1L gene.
• [5] X Liu (2021) - DNM1L variants can lead to mitochondrial fission dysfunction and neurological disorders.
• [9] Z Zhang (2024) - Three cases of encephalopathy, lethal, due to defective mitochondrial peroxisomal fission 1 caused by DNM1L gene variant were reported.