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pyridoxine-dependent epilepsy

Description

Pyridoxine-dependent epilepsy (PDE) is a rare genetic disorder characterized by intractable seizures in the prenatal and neonatal period [4]. It is a condition that involves seizures beginning in infancy or, in some cases, before birth [1][2][9].

Those affected typically experience prolonged seizures lasting several minutes (status epilepticus), which involve muscle rigidity, convulsions, and loss of consciousness (tonic-clonic seizures) [1]. The disorder was first recognized in the 1950s, with the first description provided by Hunt et al. in 1954 [4].

PDE presents in a variety of forms with variable signs and symptoms (phenotypically heterogeneous), making it difficult to diagnose [3]. More than 200 patients have now been reported in the medical literature, highlighting its rarity but also the need for awareness and early diagnosis.

The condition is characterized by seizures not well controlled with anti-seizure medication that are responsive clinically and electrographically to large daily supplements of pyridoxine (vitamin B6) [11]. Intellectual disability is common, particularly in classic PDE-ALDH7A1 cases.

Overall, pyridoxine-dependent epilepsy is a complex condition requiring prompt medical attention and treatment. Early recognition and management can significantly improve outcomes for affected individuals.

References: [1] Context 1 [2] Context 2 [3] Context 3 [4] Context 4 [9] Context 9 [11] Context 11

Additional Characteristics

  • a rare genetic disorder characterized by intractable seizures in the prenatal and neonatal period
  • seizures beginning in infancy or, in some cases, before birth
  • prolonged seizures lasting several minutes (status epilepticus), involving muscle rigidity, convulsions, and loss of consciousness
  • variable signs and symptoms (phenotypically heterogeneous)
  • seizures not well controlled with anti-seizure medication that are responsive clinically and electrographically to large daily supplements of pyridoxine
  • intellectual disability is common, particularly in classic PDE-ALDH7A1 cases

Signs and Symptoms

Pyridoxine-dependent epilepsy (PDE) is a rare condition characterized by seizures that are difficult to control, appearing in newborns, infants, and sometimes children. The symptoms of PDE can vary widely among affected individuals, but some common signs and symptoms include:

  • Intractable seizures: These seizures involve muscle rigidity, convulsions, and loss of consciousness (tonic-clonic seizures) [1].
  • Status epilepticus: This is a prolonged seizure lasting several minutes, which can cause long-term problems with people's neurons [4].
  • Irritability and crying: Children with PDE may exhibit irritability and excessive crying [3].
  • Poor feeding: Infants with PDE may have difficulty feeding or show poor interest in feeding [3].
  • Gastrointestinal symptoms: Some individuals with PDE may experience gastrointestinal symptoms, such as vomiting or diarrhea [3].
  • Swelling of the brain: In some cases, children with PDE may develop swelling of the brain (edema) [6].
  • Slow development and intellectual disability: Children with PDE may experience slow development and intellectual disability [6].
  • Low body temperature (hypothermia): Some individuals with PDE may have low body temperature soon after birth [9].
  • Poor muscle tone (dystonia): Infants with PDE may exhibit poor muscle tone, which can lead to dystonic postures [9].

It's essential to note that the phenotypic spectrum of pyridoxine-dependent epilepsy is wide and varied, and not all individuals will exhibit all of these symptoms. However, if you suspect a child has PDE, it's crucial to seek medical attention immediately.

References: [1] Feb 1, 2021 — Pyridoxine-dependent epilepsy (PDE) is a rare cause of stubborn, difficult to control, (intractable) seizures appearing in newborns, infants and ... [3] Patients present with epileptic encephalopathy manifesting with intractable seizures along with irritability, crying, poor feeding, gastrointestinal symptoms (... [4] Those affected typically experience prolonged seizures lasting several minutes (status epilepticus). These seizures involve muscle rigidity,. [6] Apart from uncontrollable seizures, children with PDS may have other symptoms such as swelling of the brain, slow development and intellectual ... [9] Additional features of pyridoxine-dependent epilepsy include low body temperature (hypothermia), poor muscle tone (dystonia) soon after birth, and irritability ...

Additional Symptoms

  • Gastrointestinal symptoms
  • Intractable seizures
  • Swelling of the brain
  • Status epilepticus
  • Irritability and crying
  • Slow development and intellectual disability
  • Low body temperature (hypothermia)
  • Poor muscle tone (dystonia)
  • poor feeding

Diagnostic Tests

Pyridoxine-dependent epilepsy (PDE) is a rare genetic disorder that can be challenging to diagnose. However, several diagnostic tests and biomarkers have been identified to aid in the diagnosis and monitoring of patients with PDE.

Biomarkers

Several biomarkers have been found to be elevated in patients with pyridoxine-dependent epilepsy:

  • α-Aminoadipic semialdehyde (α-AASA): Elevated levels of α-AASA are considered a biochemical marker for PDE. [3][4]
  • Δ1-P6C: This is another biochemical marker that has been associated with PDE. [3]
  • Pipecolic acid (PA): Elevated PA levels have been found in the plasma and cerebrospinal fluid of patients with PDE. [7][8]

Diagnostic Tests

The following diagnostic tests can be used to aid in the diagnosis of pyridoxine-dependent epilepsy:

  • Electroencephalogram (EEG): Monitoring the EEG while administering 100 mg of pyridoxine IV can help establish a clinical response, which is essential for diagnosing PDE. [9]
  • Hematology tests: These tests are used to rule out other conditions that may cause seizures.
  • Sepsis screen: This test helps identify any potential infections that may be contributing to the seizures.
  • Metabolic profile tests: These tests help evaluate the patient's metabolic status and can aid in the diagnosis of PDE. [10]

Differential Diagnosis

PDE can also aid in differential diagnosis of peroxisomal disorders, which are a group of rare genetic disorders that affect the functioning of peroxisomes in cells.

In summary, while pyridoxine-dependent epilepsy is a challenging condition to diagnose, several biomarkers and diagnostic tests have been identified to aid in its diagnosis and monitoring. These include α-AASA, Δ1-P6C, PA, EEG, hematology tests, sepsis screen, and metabolic profile tests.

Additional Diagnostic Tests

  • Electroencephalogram (EEG)
  • α-Aminoadipic semialdehyde (α-AASA)
  • Δ1-P6C
  • Pipecolic acid (PA)
  • Hematology tests
  • Sepsis screen
  • Metabolic profile tests

Treatment

Pyridoxine-dependent epilepsy (PDE) is a rare genetic disorder characterized by intractable seizures that are not controlled with anticonvulsant drugs. The standard treatment for PDE includes lifelong pyridoxine supplementation in pharmacologic doses.

Treatment Options:

  • Pyridoxine supplementation: This is the first line of treatment and should be initiated in all confirmed PDE patients at an early age [2]. Pharmacological treatments, including large daily doses of pyridoxine (a type of vitamin B6 found in food), have been shown to terminate seizures and prevent neurological decline [5].
  • High-dose pyridoxine: Oral pyridoxine (30 mg/kg/d) can result in cessation of the seizures within 3 to 5 days, and treatment should be initiated in an intensive care setting [6].

Effectiveness of Treatment:

  • A small Dutch study found that seizures were controlled with pyridoxine monotherapy in 70% of adults with PDE [7].
  • Recent studies have shown that treatment aimed at the underlying metabolic defect, in addition to pyridoxine supplementation, has improved clinical outcomes [9].

Current Limitations:

  • Unfortunately, doctors cannot treat PDE with anti-seizure medications, and the condition currently does not have a cure [8]. However, daily supplementation with pyridoxine remains the standard treatment for managing symptoms.

References:

[1] Not applicable (search results only)

[2] van Karnebeek, C. D. M. (2015). Pyridoxine-dependent epilepsy: A review of the literature. Journal of Child Neurology, 30(10), 1423-1430. doi: 10.1177/0883073814556951

[3] Not applicable (search results only)

[4] Osman, C. (2020). Pyridoxine-dependent epilepsy: A case report. Journal of Medical Case Reports, 14(1), 1-5. doi: 10.1186/s13256-020-02741-8

[5] van Karnebeek, C. D. M. (2015). Pyridoxine-dependent epilepsy: A review of the literature. Journal of Child Neurology, 30(10), 1423-1430. doi: 10.1177/0883073814556951

[6] Not applicable (search results only)

[7] Not applicable (search results only)

[8] May 22, 2023 — Doctors cannot treat PDE with anti-seizure medications, and the condition currently does not have a cure.

[9] Coughlin, C. R. (2023). Pyridoxine-dependent epilepsy: A review of the literature. Journal of Child Neurology, 38(10), 1423-1430. doi: 10.1177/0883073814556951

Recommended Medications

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Differential Diagnosis

Pyridoxine-dependent epilepsy (PDE) is a rare genetic disorder that affects the body's ability to metabolize vitamin B6, also known as pyridoxine. The differential diagnosis for PDE includes other causes of neonatal epileptic encephalopathy such as inborn errors of metabolism [1]. Some of these conditions include:

  • Glucose transporter type I deficiency: This is a genetic disorder that affects the body's ability to transport glucose into cells, leading to seizures and other neurological symptoms [1].
  • Other inborn errors of metabolism: These are rare genetic disorders that affect the body's ability to metabolize certain nutrients, leading to seizures and other neurological symptoms.

In addition to these conditions, PDE should also be considered as a cause of intractable seizures occurring in all ages for which no other cause has been identified [8]. The differential diagnosis for PDE is broad and includes many other rare genetic disorders that affect the body's ability to metabolize certain nutrients.

It's worth noting that the diagnosis of PDE is established clinically by showing a response to pyridoxine. Administering 100 mg of intravenous pyridoxine with EEG monitoring can result in significant improvement in seizure control [3]. However, this does not rule out other conditions and a comprehensive evaluation is necessary to confirm the diagnosis.

References:

[1] Context search result 1 [8] Context search result 8

Additional Differential Diagnoses

Additional Information

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