MCID: EPL131
MIFTS: 37

Epilepsy, Pyridoxine-Dependent

Categories: Genetic diseases, Rare diseases, Neuronal diseases, Metabolic diseases

Aliases & Classifications for Epilepsy, Pyridoxine-Dependent

MalaCards integrated aliases for Epilepsy, Pyridoxine-Dependent:

Name: Epilepsy, Pyridoxine-Dependent 53 24 13 69
Pyridoxine-Dependent Epilepsy 53 23 49 24 55 71 36 28
Vitamin B6-Dependent Seizures 23 49 24 55
Pyridoxine Dependency with Seizures 53 49 24
Pyridoxine Dependency 23 49 24
Pde 53 24 71
Aasa Dehydrogenase Deficiency 53 24
Pyridoxine-Dependent Seizures 23 24
Antiquitin Deficiency 49 55
Epd 53 24
Pyridoxine-Dependent Epilepsy; Pde 53

Characteristics:

Orphanet epidemiological data:

55
pyridoxine-dependent epilepsy
Inheritance: Autosomal recessive; Prevalence: 1-9/1000000 (Europe); Age of onset: Antenatal,Infancy,Neonatal; Age of death: any age,normal life expectancy;

OMIM:

53
Inheritance:
autosomal recessive

Miscellaneous:
prenatal or neonatal onset
seizures are responsive to pyridoxine treatment
incidence of 1 in 276,000 in the netherlands


HPO:

31
epilepsy, pyridoxine-dependent:
Inheritance autosomal recessive inheritance


Classifications:



External Ids:

OMIM 53 266100
Orphanet 55 ORPHA3006
MESH via Orphanet 42 C536254
UMLS via Orphanet 70 C1849508 C1291560
ICD10 via Orphanet 33 G40.8
MedGen 39 C1849508
KEGG 36 H01247
UMLS 69 C1849508

Summaries for Epilepsy, Pyridoxine-Dependent

NIH Rare Diseases : 49 Pyridoxine-dependent epilepsy is a condition that involves seizures beginning in infancy or, in some cases, before birth. Those affected typically experience prolonged seizures lasting several minutes (status epilepticus). These seizures involve muscle rigidity, convulsions, and loss of consciousness (tonic-clonic seizures). Anticonvulsant drugs, which are usually given to control seizures, are ineffective in people with pyridoxine-dependent epilepsy. Instead, people with this type of seizure are medically treated with large daily doses of pyridoxine (a type of vitamin B6 found in food). Mutations in the ALDH7A1 gene cause pyridoxine-dependent epilepsy. This gene is inherited in an autosomal recessive fashion. Last updated: 7/23/2013

MalaCards based summary : Epilepsy, Pyridoxine-Dependent, also known as pyridoxine-dependent epilepsy, is related to epilepsy and cystathioninuria, and has symptoms including intellectual disability, muscular hypotonia and neurological speech impairment. An important gene associated with Epilepsy, Pyridoxine-Dependent is ALDH7A1 (Aldehyde Dehydrogenase 7 Family Member A1), and among its related pathways/superpathways is Lysine degradation.

OMIM : 53 Pyridoxine-dependent epilepsy, characterized by a combination of various seizure types, usually occurs in the first hours of life and is unresponsive to standard anticonvulsants, responding only to immediate administration of pyridoxine hydrochloride. The dependence is permanent, and the interruption of daily pyridoxine supplementation leads to the recurrence of seizures. Some patients show developmental delay. The prevalence is estimated at 1 in 400,000 to 700,000 (Bennett et al., 2005). (266100)

UniProtKB/Swiss-Prot : 71 Pyridoxine-dependent epilepsy: Characterized by a combination of various seizure types. It usually occurs in the first hours of life and is unresponsive to standard anticonvulsants, responding only to immediate administration of pyridoxine hydrochloride.

Genetics Home Reference : 24 Pyridoxine-dependent epilepsy is a condition that involves seizures beginning in infancy or, in some cases, before birth. Those affected typically experience prolonged seizures lasting several minutes (status epilepticus). These seizures involve muscle rigidity, convulsions, and loss of consciousness (tonic-clonic seizures). Additional features of pyridoxine-dependent epilepsy include low body temperature (hypothermia), poor muscle tone (dystonia) soon after birth, and irritability before a seizure episode. In rare instances, children with this condition do not have seizures until they are 1 to 3 years old.

Wikipedia : 72 Pyridoxine-dependent epilepsy (PDE), also referred to as pyridoxine-dependent seizure (PDS) or vitamin... more...

GeneReviews: NBK1486

Related Diseases for Epilepsy, Pyridoxine-Dependent

Diseases related to Epilepsy, Pyridoxine-Dependent via text searches within MalaCards or GeneCards Suite gene sharing:

(show all 17)
# Related Disease Score Top Affiliating Genes
1 epilepsy 29.9 ALDH7A1 PLPBP
2 cystathioninuria 10.9
3 microcephaly 10.1
4 blood group, i system 10.0
5 ovarian cancer 9.9
6 postpartum depression 9.9
7 hypophosphatasia 9.9
8 folinic acid-responsive seizures 9.9
9 leukemia, chronic lymphocytic 2 9.9
10 leukemia, chronic lymphocytic 9.9
11 leukemia 9.9
12 retinitis 9.9
13 retinal degeneration 9.9
14 leukemia, b-cell, chronic 9.9
15 lung cancer 9.7
16 neuroblastoma 9.7
17 asthma 9.7

Graphical network of the top 20 diseases related to Epilepsy, Pyridoxine-Dependent:



Diseases related to Epilepsy, Pyridoxine-Dependent

Symptoms & Phenotypes for Epilepsy, Pyridoxine-Dependent

Symptoms via clinical synopsis from OMIM:

53
NeurologicCentralNervousSystem:
seizures
status epilepticus
hypotonia
mental retardation
speech delay
more
Respiratory:
respiratory distress, neonatal

LaboratoryAbnormalities:
increased serum and cerebrospinal fluid levels of pipecolic acid
increased serum, cerebrospinal fluid, and urinary levels of alpha-aminoadipic semialdehyde

PrenatalManifestations:
fetal distress

PrenatalManifestationsMovement:
abnormal intrauterine movements


Clinical features from OMIM:

266100

Human phenotypes related to Epilepsy, Pyridoxine-Dependent:

55 31 (show all 21)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 intellectual disability 55 31 hallmark (90%) Very frequent (99-80%) HP:0001249
2 muscular hypotonia 55 31 frequent (33%) Frequent (79-30%) HP:0001252
3 neurological speech impairment 55 31 hallmark (90%) Very frequent (99-80%) HP:0002167
4 eeg abnormality 55 31 hallmark (90%) Very frequent (99-80%) HP:0002353
5 global developmental delay 55 31 hallmark (90%) Very frequent (99-80%) HP:0001263
6 hepatomegaly 55 31 occasional (7.5%) Occasional (29-5%) HP:0002240
7 abnormality of metabolism/homeostasis 55 31 hallmark (90%) Very frequent (99-80%) HP:0001939
8 abnormality of movement 55 31 hallmark (90%) Very frequent (99-80%) HP:0100022
9 strabismus 55 31 occasional (7.5%) Occasional (29-5%) HP:0000486
10 ventriculomegaly 55 31 occasional (7.5%) Occasional (29-5%) HP:0002119
11 cerebral cortical atrophy 55 31 occasional (7.5%) Occasional (29-5%) HP:0002120
12 status epilepticus 55 31 hallmark (90%) Very frequent (99-80%) HP:0002133
13 seizures 55 Very frequent (99-80%)
14 respiratory distress 31 HP:0002098
15 delayed speech and language development 31 HP:0000750
16 generalized myoclonic seizures 31 HP:0002123
17 generalized tonic-clonic seizures 31 HP:0002069
18 prenatal movement abnormality 31 HP:0001557
19 neonatal respiratory distress 31 HP:0002643
20 generalized hypotonia 31 HP:0001290
21 fetal distress 31 HP:0025116

UMLS symptoms related to Epilepsy, Pyridoxine-Dependent:


myoclonic seizures, seizures

Drugs & Therapeutics for Epilepsy, Pyridoxine-Dependent

Interventional clinical trials:


# Name Status NCT ID Phase Drugs
1 Neurodevelopmental Outcome of Early Dietary Lysine Restriction in Pyridoxine Dependent Epilepsy Patients Withdrawn NCT01795170 Pyridoxine

Search NIH Clinical Center for Epilepsy, Pyridoxine-Dependent

Genetic Tests for Epilepsy, Pyridoxine-Dependent

Genetic tests related to Epilepsy, Pyridoxine-Dependent:

# Genetic test Affiliating Genes
1 Pyridoxine-Dependent Epilepsy 28 ALDH7A1

Anatomical Context for Epilepsy, Pyridoxine-Dependent

Publications for Epilepsy, Pyridoxine-Dependent

Articles related to Epilepsy, Pyridoxine-Dependent:

(show top 50) (show all 68)
# Title Authors Year
1
Obstructive Hydrocephalus in Pyridoxine-Dependent Epilepsy: An Uncommon Complication. ( 28216032 )
2017
2
A cohort study of pyridoxine-dependent epilepsy and high prevalence of splice site IVS11+1G>A mutation in Chinese patients. ( 26555630 )
2015
3
Pyridoxine-dependent epilepsy in two Turkish patients in Turkey and review of the literature. ( 27186704 )
2015
4
First cases of pyridoxine-dependent epilepsy in Bulgaria: novel mutation in the ALDH7A1 gene. ( 26232297 )
2015
5
Current treatment and management of pyridoxine-dependent epilepsy. ( 25639976 )
2015
6
Intragenic deletions of ALDH7A1 in pyridoxine-dependent epilepsy caused by Alu-Alu recombination. ( 26224730 )
2015
7
Long-Term Treatment Outcome of two Patients With Pyridoxine-Dependent Epilepsy Caused by ALDH7A1 Mutations: Normal Neurocognitive Outcome. ( 24789515 )
2014
8
Fetal onset ventriculomegaly and subependymal cysts in a pyridoxine dependent epilepsy patient. ( 24664088 )
2014
9
Seizure recurrence following pyridoxine withdrawal in a patient with pyridoxine-dependent epilepsy. ( 25123644 )
2014
10
Clinical diagnosis, treatment, and ALDH7A1 mutations in pyridoxine-dependent epilepsy in three Chinese infants. ( 24664145 )
2014
11
Novel therapy for pyridoxine dependent epilepsy due to ALDH7A1 genetic defect: l-arginine supplementation alternative to lysine-restricted diet. ( 25127453 )
2014
12
Lysine-Restricted Diet as Adjunct Therapy for Pyridoxine-Dependent Epilepsy: The PDE Consortium Consensus Recommendations. ( 24748525 )
2014
13
Overexpression of recombinant human antiquitin in E. coli: partial enzyme activity in selected ALDH7A1 missense mutations associated with pyridoxine-dependent epilepsy. ( 24613284 )
2014
14
Corpus callosum alterations in pyridoxine-dependent epilepsy: a mirror image of an ongoing disease? ( 24948334 )
2014
15
Callosal alterations in pyridoxine-dependent epilepsy. ( 24942048 )
2014
16
Early diagnosis of pyridoxine-dependent epilepsy: video-EEG monitoring and biochemical and genetic investigation. ( 23916709 )
2013
17
Pyridoxine-dependent Epilepsy: An Often Unrecognized but Treatable cause of Intractable Seizures:Case report from Korle Bu Teaching Hospital, Accra, Ghana. ( 24122693 )
2013
18
Pyridoxine-dependent epilepsy owing to antiquitin deficiency--mutation in the ALDH7A1 gene. ( 23925287 )
2013
19
Identification of a novel missense mutation in the ALDH7A1 gene in two unrelated Tunisian families with pyridoxine-dependent epilepsy. ( 23054014 )
2013
20
Long-Term Follow-up of a Successfully Treated Case of Congenital Pyridoxine-Dependent Epilepsy. ( 23430810 )
2013
21
Preliminary investigation of the use of newborn dried blood spots for screening pyridoxine-dependent epilepsy by LC-MS/MS. ( 23953072 )
2013
22
Pyridoxine-dependent epilepsy in Tunisia is caused by a founder missense mutation of the ALDH7A1 gene. ( 23376216 )
2013
23
Normal plasma pipecolic acid level in pyridoxine dependent epilepsy due to ALDH7A1 mutations. ( 23683770 )
2013
24
Pyridoxine-dependent epilepsy due to antiquitin deficiency: achieving a favourable outcome. ( 24184718 )
2013
25
Congenital cataract in a child with pyridoxine-dependent epilepsy. ( 23602455 )
2013
26
Clinical, biochemical, and molecular studies in pyridoxine-dependent epilepsy. Antisense therapy as possible new therapeutic option. ( 23350806 )
2013
27
Glial localization of antiquitin: Implications for pyridoxine-dependent epilepsy. ( 24122892 )
2013
28
Natural history of pyridoxine-dependent epilepsy: tools for prognostication. ( 22803601 )
2012
29
Overexpression of human antiquitin in E. coli: enzymatic characterization of twelve ALDH7A1 missense mutations associated with pyridoxine-dependent epilepsy. ( 22784480 )
2012
30
Profound neonatal hypoglycemia and lactic acidosis caused by pyridoxine-dependent epilepsy. ( 22529283 )
2012
31
A case of extreme prematurity and delayed diagnosis of pyridoxine-dependent epilepsy. ( 23022904 )
2012
32
Pyridoxine dependent epilepsy: enduring mystery and continuing challenges. ( 22728846 )
2012
33
Variability of phenotype in two sisters with pyridoxine dependent epilepsy. ( 22728861 )
2012
34
Pyridoxine-dependent epilepsy with elevated urinary I+-amino adipic semialdehyde in molybdenum cofactor deficiency. ( 23147983 )
2012
35
Epilepsy due to 20q13.33 subtelomere deletion masquerading as pyridoxine-dependent epilepsy. ( 23166088 )
2012
36
Lysine restricted diet for pyridoxine-dependent epilepsy: first evidence and future trials. ( 23022070 )
2012
37
Pyridoxine-dependent epilepsy: an under-recognised cause of intractable seizures. ( 21496129 )
2012
38
Clinical and genetic analysis of three Korean children with pyridoxine-dependent epilepsy. ( 22371912 )
2012
39
Atypical pyridoxine-dependent epilepsy due to a pseudoexon in ALDH7A1. ( 22305855 )
2012
40
Long-term outcome in pyridoxine-dependent epilepsy. ( 22804844 )
2012
41
Pyridoxine dependent epilepsy and antiquitin deficiency: clinical and molecular characteristics and recommendations for diagnosis, treatment and follow-up. ( 21704546 )
2011
42
Roth spots in pyridoxine dependent epilepsy. ( 22688935 )
2011
43
Biomarkers aiding diagnosis of atypical presentation of pyridoxine-dependent epilepsy. ( 21397171 )
2011
44
Novel mutations in pyridoxine-dependent epilepsy. ( 20427214 )
2011
45
Seizures and paroxysmal events: symptoms pointing to the diagnosis of pyridoxine-dependent epilepsy and pyridoxine phosphate oxidase deficiency. ( 20370816 )
2010
46
Pyridoxine-dependent epilepsy and pyridoxine phosphate oxidase deficiency: unique clinical symptoms and non-specific EEG characteristics. ( 20412262 )
2010
47
Genotypic and phenotypic spectrum of pyridoxine-dependent epilepsy (ALDH7A1 deficiency). ( 20554659 )
2010
48
The genotypic and phenotypic spectrum of pyridoxine-dependent epilepsy due to mutations in ALDH7A1. ( 20814824 )
2010
49
The EEG response to pyridoxine-IV neither identifies nor excludes pyridoxine-dependent epilepsy. ( 20887371 )
2010
50
Folinic acid-responsive seizures are identical to pyridoxine-dependent epilepsy. ( 19142996 )
2009

Variations for Epilepsy, Pyridoxine-Dependent

UniProtKB/Swiss-Prot genetic disease variations for Epilepsy, Pyridoxine-Dependent:

71
# Symbol AA change Variation ID SNP ID
1 ALDH7A1 p.Ala199Val VAR_031718 rs121912709
2 ALDH7A1 p.Glu427Gln VAR_031719 rs121912707
3 ALDH7A1 p.Gly202Val VAR_069184
4 ALDH7A1 p.Gly291Glu VAR_069185
5 ALDH7A1 p.Asn301Ile VAR_069186 rs121912711
6 ALDH7A1 p.Arg335Gln VAR_069187 rs754449549
7 ALDH7A1 p.Val395Gly VAR_069188
8 ALDH7A1 p.Ser458Asn VAR_069189

ClinVar genetic disease variations for Epilepsy, Pyridoxine-Dependent:

6 (show all 23)
# Gene Variation Type Significance SNP ID Assembly Location
1 ALDH7A1 NM_001182.4(ALDH7A1): c.1279G> C (p.Glu427Gln) single nucleotide variant Pathogenic/Likely pathogenic rs121912707 GRCh37 Chromosome 5, 125887751: 125887751
2 ALDH7A1 NM_001182.4(ALDH7A1): c.328C> T (p.Arg110Ter) single nucleotide variant Pathogenic rs121912708 GRCh37 Chromosome 5, 125919689: 125919689
3 ALDH7A1 ALDH7A1, IVS5AS, G-C, -1 single nucleotide variant Pathogenic
4 ALDH7A1 ALDH7A1, IVS3DS, T-A, +2 single nucleotide variant Pathogenic
5 ALDH7A1 NM_001182.4(ALDH7A1): c.596C> T (p.Ala199Val) single nucleotide variant Pathogenic rs121912709 GRCh37 Chromosome 5, 125912825: 125912825
6 ALDH7A1 NM_001182.4(ALDH7A1): c.1597delG (p.Ala533Profs) deletion Pathogenic rs387906574 GRCh37 Chromosome 5, 125880680: 125880680
7 ALDH7A1 NM_001182.4(ALDH7A1): c.1224T> G (p.Tyr408Ter) single nucleotide variant Pathogenic rs121912710 GRCh37 Chromosome 5, 125887806: 125887806
8 ALDH7A1 NM_001182.4(ALDH7A1): c.902A> T (p.Asn301Ile) single nucleotide variant Pathogenic rs121912711 GRCh37 Chromosome 5, 125896786: 125896786
9 ALDH7A1 ALDH7A1, 750G-A single nucleotide variant Pathogenic
10 ALDH7A1 NM_001182.4(ALDH7A1): c.1093+1G> A single nucleotide variant Pathogenic rs794727058 GRCh37 Chromosome 5, 125891622: 125891622
11 ALDH7A1 NM_001182.4(ALDH7A1): c.1513G> C (p.Gly505Arg) single nucleotide variant Pathogenic rs556400964 GRCh38 Chromosome 5, 126546376: 126546376
12 ALDH7A1 NM_001182.4(ALDH7A1): c.1193G> T (p.Gly398Val) single nucleotide variant Pathogenic rs864622557 GRCh38 Chromosome 5, 126554294: 126554294
13 ALDH7A1 NM_001182.4(ALDH7A1): c.986G> A (p.Arg329Lys) single nucleotide variant Pathogenic rs864622558 GRCh37 Chromosome 5, 125894954: 125894954
14 ALDH7A1 NM_001182.4(ALDH7A1): c.584A> G (p.Asn195Ser) single nucleotide variant Pathogenic rs372660425 GRCh38 Chromosome 5, 126577145: 126577145
15 ALDH7A1 NM_001182.4(ALDH7A1): c.834G> A (p.Val278=) single nucleotide variant Pathogenic rs201948406 GRCh37 Chromosome 5, 125903988: 125903988
16 ALDH7A1 NM_001182.4(ALDH7A1): c.1566-1G> T single nucleotide variant Pathogenic rs140845195 GRCh38 Chromosome 5, 126545020: 126545020
17 ALDH7A1 NM_001182.4(ALDH7A1): c.247-1G> C single nucleotide variant Likely pathogenic rs1060502949 GRCh38 Chromosome 5, 126592730: 126592730
18 ALDH7A1 NM_001182.4(ALDH7A1): c.530C> A (p.Ala177Glu) single nucleotide variant Pathogenic rs764417585 GRCh38 Chromosome 5, 126577199: 126577199
19 ALDH7A1 NM_001182.4(ALDH7A1): c.589C> T (p.Pro197Ser) single nucleotide variant Pathogenic/Likely pathogenic rs779652673 GRCh37 Chromosome 5, 125912832: 125912832
20 ALDH7A1 NM_001182.4(ALDH7A1): c.1200+1G> T single nucleotide variant Likely pathogenic GRCh38 Chromosome 5, 126554286: 126554286
21 ALDH7A1 NM_001182.4(ALDH7A1): c.796C> T (p.Arg266Ter) single nucleotide variant Pathogenic GRCh37 Chromosome 5, 125904026: 125904026
22 ALDH7A1 NM_001182.4(ALDH7A1): c.532_542delCTGATTGAGCA (p.Leu178Valfs) deletion Pathogenic rs765119568 GRCh37 Chromosome 5, 125912879: 125912889
23 ALDH7A1 NM_001182.4(ALDH7A1): c.192+3A> T single nucleotide variant Likely pathogenic rs773814169 GRCh37 Chromosome 5, 125930696: 125930696

Expression for Epilepsy, Pyridoxine-Dependent

Search GEO for disease gene expression data for Epilepsy, Pyridoxine-Dependent.

Pathways for Epilepsy, Pyridoxine-Dependent

Pathways related to Epilepsy, Pyridoxine-Dependent according to KEGG:

36
# Name Kegg Source Accession
1 Lysine degradation hsa00310

GO Terms for Epilepsy, Pyridoxine-Dependent

Sources for Epilepsy, Pyridoxine-Dependent

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
16 ExPASy
18 FMA
27 GO
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29 HGMD
30 HMDB
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32 ICD10
33 ICD10 via Orphanet
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35 IUPHAR
36 KEGG
37 LifeMap
39 MedGen
41 MeSH
42 MESH via Orphanet
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58 PubMed
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65 SNOMED-CT via HPO
66 SNOMED-CT via Orphanet
67 TGDB
68 Tocris
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70 UMLS via Orphanet
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