pyridoxamine 5'-phosphate oxidase deficiency

Pyridoxamine 5'-phosphate oxidase (PNPO) deficiency is a rare genetic disorder that affects the metabolism of vitamin B6, leading to severe neurological symptoms.

Causes and Symptoms

• PNPO deficiency is an autosomal recessive condition, meaning it is inherited from both parents in a recessive pattern [1].
• The disorder results in a decrease of the active form of vitamin B6, pyridoxal 5'-phosphate (PLP), leading to reduced activity of various enzymes and proteins that rely on PLP for proper function [2].
• Symptoms typically manifest at birth or shortly thereafter, with severe seizures being a hallmark of the condition [3].
• Other symptoms may include slow heart rate and lack of oxygen before birth [1].

Treatment and Response

• PNPO deficiency is responsive to treatment with pyridoxal-5-phosphate (PLP), which can help alleviate symptoms and improve outcomes [4].
• However, seizures associated with this condition are often refractory to treatment, meaning they do not respond well to standard seizure medications [9].

References

[1] Context result 1: Some babies with PNPO deficiency will experience seizures before birth, and some will experience a slow heart rate and a lack of oxygen before ...

[2] Context result 2: Pyridoxamine Phosphate Oxidase is an enzyme deficiency that results in a decrease of the active form of vitamin B6, leading to reduced activity of various enzymes...

[3] Context result 3: PNPOD is an autosomal recessive inborn error of metabolism resulting in vitamin B6 deficiency that manifests as neonatal-onset severe seizures ...

[4] Context result 4: The PNPO gene provides instructions for producing an enzyme called pyridox(am)ine 5'-phosphate oxidase. This enzyme is involved in the breakdown (metabolism)...

[9] Context result 9: Pyridoxamine-5-phosphate oxidase deficiency results in treatment-refractory neonatal seizures that respond to treatment with pyridoxal-5-phosphate, but not...

Pyridoxamine 5'-phosphate oxidase deficiency, also known as PNPO deficiency, is a rare genetic disorder that affects the metabolism of vitamin B6 (pyridoxine). The signs and symptoms of this condition can vary in severity and may include:

• Seizures: Repeated seizures or epilepsy are a hallmark symptom of PNPO deficiency. These seizures can begin within the first two weeks of life and may be resistant to anticonvulsant medications.
• Neonatal lethargy: Infants with PNPO deficiency may exhibit lethargy, which is a state of reduced activity or alertness.
• Weight loss: Affected infants may experience weight loss due to metabolic derangement.
• Metabolic derangement: PNPO deficiency can lead to disturbances in metabolism, including hypoglycemia (low blood sugar) and hyperlactacidemia (elevated lactate levels).
• Progressive neurologic signs: Infants with PNPO deficiency may exhibit progressive neurological signs, such as alterations in muscle tone (hypotonia or hypertonia).

These symptoms can be severe and may require immediate medical attention. It's essential to note that the severity of the condition can vary among individuals, and some people may experience milder symptoms.

References:

• [1] Classic PNPO deficiency typically presents with seizures beginning on the first day of life (result 3).
• [2] Infants show lethargy, weight loss, metabolic derangement, and progressive neurologic signs (result 4).
• [3] Seizures often begin within the first two weeks of life in classic PNPO deficiency (results 1 & 10).

Pyridoxamine 5'-phosphate oxidase deficiency, also known as PNPO deficiency, can be diagnosed through various tests.

Biochemical tests: These include the measurement of specific biomarkers such as α-AASA and pipecolic acid (PA) in urine, plasma, and cerebrospinal fluid (CSF). These tests can help identify the presence of the condition [1].

Molecular genetic testing: This involves analyzing the PNPO gene to confirm the diagnosis. The PNPO gene provides instructions for producing an enzyme called pyridox(am)ine 5'-phosphate oxidase, which is involved in the breakdown (metabolism) of vitamin B6 [7]. Molecular genetic testing can help identify mutations in the PNPO gene that are associated with the condition.

Other tests: Laboratory studies may also be performed to rule out other conditions. For example, blood tests may show anemia, leukopenia, thrombocytopenia, and coagulopathy [9].

It's worth noting that there is no diagnostic biomarker for PNPO deficiency, and molecular testing is required for diagnosis [6]. However, cerebrospinal fluid (CSF) PLP was found to be low in individuals with the condition [6].

References: [1] - Suggestive Findings. [6] - by M Alghamdi · 2021 · Cited by 39 — [7] - Mar 27, 2024 — [9] - Pyridoxamine 5'-phosphate oxidase deficiency, 610090, AR, 3, PNPO, 603287 ...

Pyridoxamine 5'-phosphate oxidase (PNPO) deficiency is a rare genetic disorder that affects the metabolism of vitamin B6, leading to severe neonatal seizures and other neurological symptoms. The good news is that this condition can be effectively treated with medication.

Treatment Overview

The primary treatment for PNPO deficiency is supplementation with pyridoxal 5'-phosphate (PLP), the active form of vitamin B6 [4][8]. This has been shown to be highly effective in resolving seizures and improving neurological outcomes in affected individuals.

Specific Treatment Details

• Pyridoxal 5'-Phosphate (PLP): PLP is typically given orally, divided into 4-6 single daily doses [4].
• Dosage: The dosage of PLP may vary depending on the individual's response to treatment and their specific needs.
• Response to Treatment: Most patients with PNPO deficiency have shown a significant improvement in seizure control and neurological function after starting PLP supplementation.

Additional Information

It is essential to note that conventional antiepileptic drugs are often ineffective in treating seizures associated with PNPO deficiency [6]. Therefore, early diagnosis and initiation of PLP therapy are crucial for optimal outcomes.

In some cases, patients may also benefit from targeted therapy, such as pharmacologic treatment with PLP [4].

References

[4] by B Plecko · 2022 · Cited by 10 — Targeted therapy: Pharmacologic treatment: PLP, the active form of vitamin B6, is typically given orally, divided into 4-6 single daily doses. [6] by PY Chen · 2019 · Cited by 10 — The clinical phenotypes do not respond to antiepileptic drugs but respond to PLP. [8] Pyridoxal-5'-phosphate oxidase (PNPO) deficiency is a rare autosomal recessive, vitamin-responsive metabolic disorder causing refractory neonatal seizures that respond to the administration of pyridoxal-5'-phosphate (PLP).

Pyridoxamine 5'-phosphate oxidase (PNPO) deficiency is a rare genetic disorder that can be challenging to diagnose, especially in the neonatal period. However, there are certain conditions and factors that should be considered in the differential diagnosis of PNPO deficiency.

Classic Presentation

In about 90% of affected individuals, PNPO deficiency presents with classic symptoms, including:

• Seizures that commence on the first day of life
• EEG showing a burst suppression pattern
• Premature birth
• Fetal seizures

These symptoms are often resistant to anticonvulsant drugs and can be fatal if left untreated.

Other Conditions to Consider

In addition to PNPO deficiency, other conditions that may present with similar symptoms include:

• Pyridoxine-dependent epilepsy (PDE) caused by changes in the ALDH7A1 gene
• PLPBP deficiency caused by changes in the PLPBP gene

These conditions are also characterized by seizures and can be responsive to pyridoxal phosphate (PLP) or pyridoxine supplementation.

Key Diagnostic Features

To diagnose PNPO deficiency, it is essential to consider the following key features:

• Low levels of pyridoxal phosphate in the brain
• Inadequate production of PLP due to dysfunctional variants of the PNPO gene
• Seizures that are resistant to anticonvulsant drugs and can be fatal if left untreated

Treatment and Management

The treatment of choice for PNPO deficiency is supplementation with pyridoxal phosphate (PLP) or pyridoxine, which has been shown to provide seizure control in all examined cases.

In conclusion, PNPO deficiency is a rare genetic disorder that requires prompt recognition and diagnosis. By considering the classic presentation, other conditions to rule out, key diagnostic features, and treatment options, healthcare providers can ensure timely and effective management of this condition.

References:

• [3] Pyridoxamine-5′-phosphate oxidase (PNPO) deficiency is a recently recognized autosomal recessive neonatal epileptic encephalopathy (MIM 601142).
• [10] In classic PNPO deficiency, seizures often begin on the first day of life and typically respond to pyridoxal phosphate (PLP) supplementation.
• [13] Pyridoxamine-5′-phosphate oxidase (PNPO) deficiency is an autosomal recessive epileptic encephalopathy responsive to pyridoxal 5′-phosphate (PLP).
• [14] Pyridox (am)ine- 5- phosphate oxidase (PNPO) deficiency is a vitamin-responsive epilepsy syndrome that poses significant challenges in management.