Pyridoxamine 5-prime-phosphate oxidase deficiency: Difference between revisions
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{{Infobox_Disease | | {{Infobox_Disease | | ||
Name = {{PAGENAME}} | | Name = {{PAGENAME}} | | ||
ICD10 = | ICD10 = {{ICD10|G|40|8}}| | ||
OMIM = 610090| | OMIM = 610090| | ||
}} | }} | ||
{{SI}} | {{SI}} | ||
{{CMG}} | {{CMG}}; {{AE}} {{ADI}} | ||
{{SK}} PNPO deficiency; PNPO-related neonatal epileptic encephalopathy; pyridoxamine 5-prime-phosphate oxidase deficiency; pyridoxine-5'-phosphate oxidase deficiency | {{SK}} PNPO deficiency; PNPO-related neonatal epileptic encephalopathy; pyridoxamine 5-prime-phosphate oxidase deficiency; pyridoxine-5'-phosphate oxidase deficiency | ||
==Overview== | ==Overview== | ||
Pyridoxal 5'-phosphate-dependent epilepsy is a rare condition | 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. <ref name="urlPyridoxal 5-phosphate-dependent epilepsy - Genetics Home Reference">{{cite web |url=http://ghr.nlm.nih.gov/condition/pyridoxal-5-phosphate-dependent-epilepsy |title=Pyridoxal 5'-phosphate-dependent epilepsy - Genetics Home Reference |format= |work= |accessdate=}}</ref> | ||
==Pathophysiology== | ==Pathophysiology== | ||
===Genetics=== | ===Genetics=== | ||
Pyridoxine 5' phosphate oxidase is an enzyme involved in conversion of dietary B6 to its active form pyridoxal 5' phosphate(PLP). 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. This results in disturbances in neurotransmitters in the brain and can cause seizures. This disease is inherited in a autosomal recessive fashion. | Pyridoxine 5' phosphate oxidase is an enzyme involved in conversion of dietary [[vitamin B6]] to its active form pyridoxal 5' phosphate(PLP)<ref name="pmid22201923">{{cite journal |author=di Salvo ML, Safo MK, Contestabile R |title=Biomedical aspects of pyridoxal 5'-phosphate availability |journal=Front Biosci (Elite Ed) |volume=4 |issue= |pages=897–913 |year=2012 |pmid=22201923 |doi= |url=}}</ref>. 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<ref name="pmid15772097">{{cite journal |author=Mills PB, Surtees RA, Champion MP, ''et al.'' |title=Neonatal epileptic encephalopathy caused by mutations in the PNPO gene encoding pyridox(am)ine 5'-phosphate oxidase |journal=Hum. Mol. Genet. |volume=14 |issue=8 |pages=1077–86 |year=2005 |month=April |pmid=15772097 |doi=10.1093/hmg/ddi120 |url=}}</ref>. This results in disturbances in [[neurotransmitters]] in the[[ brain]] and can cause [[seizures]]. This disease is inherited in a [[autosomal recessive]] fashion. | ||
==Epidemiology and Demographics== | ==Epidemiology and Demographics== | ||
Pyridoxamine 5-prime-phosphate oxidase deficiency | Pyridoxamine 5-prime-phosphate oxidase deficiency is a rare disease. Only 14 cases have been reported so far.<ref name="urlPyridoxal 5-phosphate-dependent epilepsy - Genetics Home Reference">{{cite web |url=http://ghr.nlm.nih.gov/condition/pyridoxal-5-phosphate-dependent-epilepsy |title=Pyridoxal 5'-phosphate-dependent epilepsy - Genetics Home Reference |format= |work= |accessdate=}}</ref> | ||
==Natural History, Complications and Prognosis== | |||
Babies are born in [[fetal distress|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==== | |||
* [[Seizures]] | |||
* [[Confusion]] | |||
===Laboratory Findings=== | |||
====Electrolyte and Biomarker Studies==== | |||
* Low levels of [[pyidoxal 5' phosphate]]. | |||
* Increase in blood [[lactate]] levels may be seen. | |||
* [[Hypoglycemia|Decrease in blood glucose levels]]. | |||
* [[Metabolic acidosis]] may be seen. | |||
====Electroencephalogram==== | |||
EEG findings are<ref name="pmid21292558">{{cite journal |author=Veerapandiyan A, Winchester SA, Gallentine WB, ''et al.'' |title=Electroencephalographic and seizure manifestations of pyridoxal 5'-phosphate-dependent epilepsy |journal=Epilepsy Behav |volume=20 |issue=3 |pages=494–501 |year=2011 |month=March |pmid=21292558 |doi=10.1016/j.yebeh.2010.12.046 |url=}}</ref> | |||
* Inter ictal burst suppression | |||
* Multifocal independent sharp waves | |||
* Electrical [[status epilepticus]] in sleep | |||
====Genetic Tests==== | |||
A few genetic tests are available<ref name="urlC1864723[DISCUI] - Tests - GTR - NCBI">{{cite web |url=http://www.ncbi.nlm.nih.gov/gtr/tests/?term=C1864723[DISCUI]&display_string=Pyridoxal%205%27-phosphate-dependent%20epilepsy&condition=C1864723 |title=C1864723[DISCUI] - Tests - GTR - NCBI |format= |work= |accessdate=}}</ref> | |||
* 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== | ==References== | ||
{{reflist|2}} | {{reflist|2}} | ||
| Line 28: | Line 79: | ||
[[Category:Disease]] | [[Category:Disease]] | ||
[[Category:Grammar]] | [[Category:Grammar]] | ||
[[Category:Genetic diseases]] | |||
[[Category:Rare diseases]] | |||
Latest revision as of 20:27, 2 August 2012
| Pyridoxamine 5-prime-phosphate oxidase deficiency | |
| ICD-10 | G40.8 |
|---|---|
| OMIM | 610090 |
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".