Pyridoxamine 5-prime-phosphate oxidase deficiency
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Aditya Govindavarjhulla, M.B.B.S. [2]
Synonyms and keywords: PNPO deficiency; PNPO-related neonatal epileptic encephalopathy; pyridoxamine 5-prime-phosphate oxidase deficiency; pyridoxine-5′-phosphate oxidase deficiency
Overview
Pyridoxal 5′-phosphate-dependent epilepsy is a rare condition. It is a condition that involves seizures beginning soon after birth or, in some cases, before birth. [1]
Pathophysiology
Genetics
Pyridoxine 5′ phosphate oxidase is an enzyme involved in conversion of dietary vitamin B6 to its active form pyridoxal 5′ phosphate(PLP)[2]. This active form of vitamin B6 is useful in the metabolism of proteins and neurotransmitters of brain. PNPO gene mutations result in a pyridoxine 5′ phosphate oxidase enzyme that is unable to metabolize pyridoxine and pyridoxamine, leading to a deficiency of PLP[3]. This results in disturbances in neurotransmitters in thebrain and can cause seizures. This disease is inherited in a autosomal recessive fashion.
Epidemiology and Demographics
Pyridoxamine 5-prime-phosphate oxidase deficiency is a rare disease. Only 14 cases have been reported so far.[1]
Natural History, Complications and Prognosis
Babies are born in distress and seizures can be noticed within few hours of birth.
Complications
- Seizures
- Encephalopathy
- Developmental delay
- Neurological problems
- Learning disorder
- Coma
- Death
Diagnosis
History
A detailed antenatal history and family history for genetic diseases may be helpful in excluding other diagnosis.
Physical Examination
Appearance of the patients
Patient may be in distress.
Eyes
- Staring gaze may be noticed.
Heart
- Slow heart rate(Bradycardia) may be seen.
Neurologic
Laboratory Findings
Electrolyte and Biomarker Studies
- Low levels of pyidoxal 5′ phosphate.
- Increase in blood lactate levels may be seen.
- Decrease in blood glucose levels.
- Metabolic acidosis may be seen.
Electroencephalogram
EEG findings are[4]
- Inter ictal burst suppression
- Multifocal independent sharp waves
- Electrical status epilepticus in sleep
Genetic Tests
A few genetic tests are available[5]
- Genetic analysis for PNPO gene mutations.
- Sequence analysis for entire codon region.
Treatment
Medical Therapy
- Unresponsive to anticonvulsant therapy.
- May respond to pyridoxal phosphate administration.
- Care about airway, breathing and circulation has to be taken care as child has tendency for seizures.
- Monitoring of blood glucose is required as the encephalopathy may worsen with hypoglycemia.
References
- ↑ 1.0 1.1 “Pyridoxal 5′-phosphate-dependent epilepsy – Genetics Home Reference”.
- ↑ di Salvo ML, Safo MK, Contestabile R (2012). “Biomedical aspects of pyridoxal 5′-phosphate availability”. Front Biosci (Elite Ed). 4: 897–913. PMID 22201923.
- ↑ Mills PB, Surtees RA, Champion MP; et al. (2005). “Neonatal epileptic encephalopathy caused by mutations in the PNPO gene encoding pyridox(am)ine 5′-phosphate oxidase”. Hum. Mol. Genet. 14 (8): 1077–86. doi:10.1093/hmg/ddi120. PMID 15772097. Unknown parameter
|month=ignored (help) - ↑ Veerapandiyan A, Winchester SA, Gallentine WB; et al. (2011). “Electroencephalographic and seizure manifestations of pyridoxal 5′-phosphate-dependent epilepsy”. Epilepsy Behav. 20 (3): 494–501. doi:10.1016/j.yebeh.2010.12.046. PMID 21292558. Unknown parameter
|month=ignored (help) - ↑ “C1864723[DISCUI] – Tests – GTR – NCBI”.
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