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)<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. | 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== | ||
| Line 22: | Line 22: | ||
==Natural History, Complications and Prognosis== | ==Natural History, Complications and Prognosis== | ||
Babies are born | Babies are born in [[fetal distress|distress]] and [[seizures]] can be noticed within few hours of birth. | ||
===Complications=== | ===Complications=== | ||
* [[Seizures]] | * [[Seizures]] | ||
| Line 31: | Line 31: | ||
* [[Coma]] | * [[Coma]] | ||
* [[Death]] | * [[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== | ||
| Line 39: | 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".