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Pyridoxine-dependent epilepsy(EPD)

MedGen UID:
340341
Concept ID:
C1849508
Disease or Syndrome
Synonyms: EPD; Pyridoxine dependency; Pyridoxine dependency with seizures; Pyridoxine-Dependent Seizures; Vitamin B6-dependent seizures
Modes of inheritance:
Autosomal recessive inheritance
MedGen UID:
141025
Concept ID:
C0441748
Intellectual Product
Sources: HPO, OMIM, Orphanet
A mode of inheritance that is observed for traits related to a gene encoded on one of the autosomes (i.e., the human chromosomes 1-22) in which a trait manifests in homozygotes. In the context of medical genetics, autosomal recessive disorders manifest in homozygotes (with two copies of the mutant allele) or compound heterozygotes (whereby each copy of a gene has a distinct mutant allele).
Autosomal recessive inheritance (HPO, OMIM, Orphanet)
 
Gene (location): ALDH7A1 (5q23.2)
OMIM®: 266100
Orphanet: ORPHA3006

Disease characteristics

Excerpted from the GeneReview: Pyridoxine-Dependent Epilepsy
Pyridoxine-dependent epilepsy is characterized by intractable seizures within the first weeks to months of life that are not controlled with antiepileptic drugs but respond both clinically and electrographically to large daily supplements of pyridoxine (vitamin B6). Multiple types of clinical seizures have been reported in individuals with pyridoxine-dependent epilepsy. Dramatic presentations consisting of prolonged seizures and recurrent episodes of status epilepticus are typical; recurrent self-limited events including partial seizures, generalized seizures, atonic seizures, myoclonic events, and infantile spasms also occur. Affected individuals may have electrographic seizures without clinical correlates. Infants with the classic neonatal presentation begin to experience seizures soon after birth. Atypical features include: late-onset seizures (seizures that begin from late infancy up until age 3 years); seizures that initially respond to antiepileptic drugs and then become intractable; seizures during early life that do not respond to pyridoxine but are then controlled with pyridoxine several months later; and prolonged seizure-free intervals (≤5.5 months) that occur after discontinuation of pyridoxine. Intellectual disability is common. Elevated concentration of α-aminoadipic semialdehyde (α-AASA) in urine and plasma is a strong biomarker of the disorder; pipecolic acid may also be elevated in plasma and cerebrospinal fluid. [from GeneReviews]
Authors:
Sidney M Gospe   view full author information

Additional descriptions

From OMIM
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).  http://www.omim.org/entry/266100
From GHR
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.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). If left untreated, people with this condition can develop severe brain dysfunction (encephalopathy). Even though seizures can be controlled with pyridoxine, neurological problems such as developmental delay and learning disorders may still occur.  https://ghr.nlm.nih.gov/condition/pyridoxine-dependent-epilepsy

Clinical features

Fetal distress
MedGen UID:
5164
Concept ID:
C0015930
Disease or Syndrome
A nonreassuring fetal status (NRFS) indicating that the FETUS is compromised (American College of Obstetricians and Gynecologists 1988). It can be identified by sub-optimal values in FETAL HEART RATE; oxygenation of FETAL BLOOD; and other parameters.
Status epilepticus
MedGen UID:
11586
Concept ID:
C0038220
Disease or Syndrome
A life-threatening situation in which the brain is in a continuous state of seizure.
Delayed speech and language development
MedGen UID:
105318
Concept ID:
C0454644
Finding
A degree of language development that is significantly below the norm for a child of a specified age.
Respiratory distress
MedGen UID:
96907
Concept ID:
C0476273
Sign or Symptom
A pathological increase in the effort and frequency of breathing movements.
Generalized tonic-clonic seizures
MedGen UID:
141670
Concept ID:
C0494475
Disease or Syndrome
A generalized tonic-clinic seizure, characterized by loss of consciousness. This type of seizure may be preceded by an aura and is frequently followed by a period of confusion and lethargy (post-ictal state).
Global developmental delay
MedGen UID:
107838
Concept ID:
C0557874
Finding
A delay in the achievement of motor or mental milestones in the domains of development of a child, including motor skills, speech and language, cognitive skills, and social and emotional skills. This term should only be used to describe children younger than five years of age.
Prenatal movement abnormality
MedGen UID:
340343
Concept ID:
C1849510
Finding
An abnormality of fetal movement.
Generalized hypotonia
MedGen UID:
346841
Concept ID:
C1858120
Finding
Generalized muscular hypotonia (abnormally low muscle tone).
Intellectual disability
MedGen UID:
811461
Concept ID:
C3714756
Mental or Behavioral Dysfunction
Subnormal intellectual functioning which originates during the developmental period. Intellectual disability, previously referred to as mental retardation, has been defined as an IQ score below 70.
Generalized myoclonic seizures
MedGen UID:
892704
Concept ID:
C4021759
Disease or Syndrome
Seizures with sudden, brief (< 100 msec) involuntary single or multiple contraction(s) of muscles(s) or muscle groups of variable topography (axial, proximal limb, distal).
Abnormality of metabolism/homeostasis
MedGen UID:
867398
Concept ID:
C4021768
Finding
Neonatal respiratory distress
MedGen UID:
924182
Concept ID:
C4281993
Finding
Respiratory difficulty as newborn.

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • CROGVPyridoxine-dependent epilepsy
Follow this link to review classifications for Pyridoxine-dependent epilepsy in Orphanet.

Recent clinical studies

Etiology

Al Teneiji A, Bruun TU, Cordeiro D, Patel J, Inbar-Feigenberg M, Weiss S, Struys E, Mercimek-Mahmutoglu S
Metab Brain Dis 2017 Apr;32(2):443-451. Epub 2016 Nov 23 doi: 10.1007/s11011-016-9933-8. PMID: 27882480
Yuzyuk T, Thomas A, Viau K, Liu A, De Biase I, Botto LD, Pasquali M, Longo N
Mol Genet Metab 2016 Jul;118(3):167-72. Epub 2016 May 8 doi: 10.1016/j.ymgme.2016.04.015. PMID: 27324284
Mahajnah M, Corderio D, Austin V, Herd S, Mutch C, Carter M, Struys E, Mercimek-Mahmutoglu S
Pediatr Neurol 2016 Jul;60:60-5. Epub 2016 Apr 13 doi: 10.1016/j.pediatrneurol.2016.03.008. PMID: 27212567
Gül-Mert G, İncecik F, Hergüner MÖ, Ceylaner S, Altunbaşak Ş
Turk J Pediatr 2015 Jul-Aug;57(4):394-397. PMID: 27186704
Tamaura M, Shimbo H, Iai M, Yamashita S, Osaka H
Brain Dev 2015 Apr;37(4):442-5. Epub 2014 Aug 7 doi: 10.1016/j.braindev.2014.07.008. PMID: 25123644

Diagnosis

Marguet F, Barakizou H, Tebani A, Abily-Donval L, Torre S, Bayoudh F, Jebnoun S, Brasseur-Daudruy M, Marret S, Laquerriere A, Bekri S
Metab Brain Dis 2016 Dec;31(6):1435-1443. Epub 2016 Jul 20 doi: 10.1007/s11011-016-9869-z. PMID: 27438048
Yuzyuk T, Thomas A, Viau K, Liu A, De Biase I, Botto LD, Pasquali M, Longo N
Mol Genet Metab 2016 Jul;118(3):167-72. Epub 2016 May 8 doi: 10.1016/j.ymgme.2016.04.015. PMID: 27324284
van Karnebeek CD, Tiebout SA, Niermeijer J, Poll-The BT, Ghani A, Coughlin CR 2nd, Van Hove JL, Richter JW, Christen HJ, Gallagher R, Hartmann H, Stockler-Ipsiroglu S
Pediatr Neurol 2016 Jun;59:6-12. Epub 2016 Jan 11 doi: 10.1016/j.pediatrneurol.2015.12.013. PMID: 26995068
Tincheva S, Todorov T, Todorova A, Georgieva R, Stamatov D, Yordanova I, Kadiyska T, Georgieva B, Bojidarova M, Tacheva G, Litvinenko I, Mitev V
Neurol Sci 2015 Dec;36(12):2209-12. Epub 2015 Aug 1 doi: 10.1007/s10072-015-2338-3. PMID: 26232297
Tamaura M, Shimbo H, Iai M, Yamashita S, Osaka H
Brain Dev 2015 Apr;37(4):442-5. Epub 2014 Aug 7 doi: 10.1016/j.braindev.2014.07.008. PMID: 25123644

Therapy

Al Teneiji A, Bruun TU, Cordeiro D, Patel J, Inbar-Feigenberg M, Weiss S, Struys E, Mercimek-Mahmutoglu S
Metab Brain Dis 2017 Apr;32(2):443-451. Epub 2016 Nov 23 doi: 10.1007/s11011-016-9933-8. PMID: 27882480
Marguet F, Barakizou H, Tebani A, Abily-Donval L, Torre S, Bayoudh F, Jebnoun S, Brasseur-Daudruy M, Marret S, Laquerriere A, Bekri S
Metab Brain Dis 2016 Dec;31(6):1435-1443. Epub 2016 Jul 20 doi: 10.1007/s11011-016-9869-z. PMID: 27438048
Yuzyuk T, Thomas A, Viau K, Liu A, De Biase I, Botto LD, Pasquali M, Longo N
Mol Genet Metab 2016 Jul;118(3):167-72. Epub 2016 May 8 doi: 10.1016/j.ymgme.2016.04.015. PMID: 27324284
Mahajnah M, Corderio D, Austin V, Herd S, Mutch C, Carter M, Struys E, Mercimek-Mahmutoglu S
Pediatr Neurol 2016 Jul;60:60-5. Epub 2016 Apr 13 doi: 10.1016/j.pediatrneurol.2016.03.008. PMID: 27212567
Tincheva S, Todorov T, Todorova A, Georgieva R, Stamatov D, Yordanova I, Kadiyska T, Georgieva B, Bojidarova M, Tacheva G, Litvinenko I, Mitev V
Neurol Sci 2015 Dec;36(12):2209-12. Epub 2015 Aug 1 doi: 10.1007/s10072-015-2338-3. PMID: 26232297

Prognosis

Marguet F, Barakizou H, Tebani A, Abily-Donval L, Torre S, Bayoudh F, Jebnoun S, Brasseur-Daudruy M, Marret S, Laquerriere A, Bekri S
Metab Brain Dis 2016 Dec;31(6):1435-1443. Epub 2016 Jul 20 doi: 10.1007/s11011-016-9869-z. PMID: 27438048
Coughlin CR 2nd, van Karnebeek CD, Al-Hertani W, Shuen AY, Jaggumantri S, Jack RM, Gaughan S, Burns C, Mirsky DM, Gallagher RC, Van Hove JL
Mol Genet Metab 2015 Sep-Oct;116(1-2):35-43. Epub 2015 May 23 doi: 10.1016/j.ymgme.2015.05.011. PMID: 26026794
Tamaura M, Shimbo H, Iai M, Yamashita S, Osaka H
Brain Dev 2015 Apr;37(4):442-5. Epub 2014 Aug 7 doi: 10.1016/j.braindev.2014.07.008. PMID: 25123644
Badoe EV
West Afr J Med 2013 Jul-Sep;32(3):231-4. PMID: 24122693
Bok LA, Halbertsma FJ, Houterman S, Wevers RA, Vreeswijk C, Jakobs C, Struys E, Van Der Hoeven JH, Sival DA, Willemsen MA
Dev Med Child Neurol 2012 Sep;54(9):849-54. Epub 2012 Jul 13 doi: 10.1111/j.1469-8749.2012.04347.x. PMID: 22804844

Clinical prediction guides

Al Teneiji A, Bruun TU, Cordeiro D, Patel J, Inbar-Feigenberg M, Weiss S, Struys E, Mercimek-Mahmutoglu S
Metab Brain Dis 2017 Apr;32(2):443-451. Epub 2016 Nov 23 doi: 10.1007/s11011-016-9933-8. PMID: 27882480
Yuzyuk T, Thomas A, Viau K, Liu A, De Biase I, Botto LD, Pasquali M, Longo N
Mol Genet Metab 2016 Jul;118(3):167-72. Epub 2016 May 8 doi: 10.1016/j.ymgme.2016.04.015. PMID: 27324284
Poliachik SL, Friedman SD, Poliakov AV, Budech CB, Ishak GE, Shaw DW, Gospe SM Jr
Pediatr Neurol 2016 Jan;54:43-8. Epub 2015 Sep 25 doi: 10.1016/j.pediatrneurol.2015.09.012. PMID: 26547255
Coughlin CR 2nd, van Karnebeek CD, Al-Hertani W, Shuen AY, Jaggumantri S, Jack RM, Gaughan S, Burns C, Mirsky DM, Gallagher RC, Van Hove JL
Mol Genet Metab 2015 Sep-Oct;116(1-2):35-43. Epub 2015 May 23 doi: 10.1016/j.ymgme.2015.05.011. PMID: 26026794
Bok LA, Halbertsma FJ, Houterman S, Wevers RA, Vreeswijk C, Jakobs C, Struys E, Van Der Hoeven JH, Sival DA, Willemsen MA
Dev Med Child Neurol 2012 Sep;54(9):849-54. Epub 2012 Jul 13 doi: 10.1111/j.1469-8749.2012.04347.x. PMID: 22804844

Recent systematic reviews

Scharer G, Brocker C, Vasiliou V, Creadon-Swindell G, Gallagher RC, Spector E, Van Hove JL
J Inherit Metab Dis 2010 Oct;33(5):571-81. Epub 2010 Sep 3 doi: 10.1007/s10545-010-9187-2. PMID: 20814824Free PMC Article

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