Details of Disease

General Information of Disease (ID: DISVYADQ)

• Disease Name: Pyridoxine-dependent epilepsy
• Synonyms: EPD; AASA dehydrogenase deficiency; pyridoxine dependency; epilepsy, pyridoxine-dependent; Epd; pyridoxine dependency with seizures; pyridoxine-dependent epilepsy; antiquitin deficiency; vitamin B6-dependent seizures
• Definition: A rare neurometabolic disease characterized by recurrent intractable seizures in the prenatal, neonatal and postnatal period that are resistant to anti-epileptic drugs (AEDs) but that are responsive to pharmacological dosages of pyridoxine (vitamin B6).
• Disease Hierarchy:
  DISOEVKS: Metabolic epilepsy
  DIS625V0: Inborn disorder of pyridoxine metabolism
  DISD715V: Hereditary neurological disease
  DISVYADQ: Pyridoxine-dependent epilepsy
• Disease Identifiers:
  MONDO ID: MONDO_0009945
  MESH ID: C536254
  UMLS CUI: C1849508
  OMIM ID: 266100
  MedGen ID: 340341
  Orphanet ID: 3006
  SNOMED CT ID: 734434007

Drug-Interaction Atlas (DIA) of This Disease

This Disease is Treated as An Indication in 1 Approved Drug(s)

Drug Name	Drug ID	Highest Status	Drug Type	REF
Vitamin B6	DMDBZMV	Approved	Small molecular drug	[1]

Molecular Interaction Atlas (MIA) of This Disease

This Disease Is Related to 4 DTT Molecule(s)

Gene Name	DTT ID	Evidence Level	Mode of Inheritance	REF
PRKG1	TT7IZSA	Limited	Biomarker	[2]
GLUL	TTURQ2G	Strong	Biomarker	[3]
GUCY2C	TTLDPRG	Strong	Biomarker	[4]
SLC13A5	TTFIMH7	Strong	GermlineCausalMutation	[5]

This Disease Is Related to 1 DTP Molecule(s)

Gene Name	DTP ID	Evidence Level	Mode of Inheritance	REF
SLC13A5	DTFPWJ9	Supportive	Autosomal recessive	[5]

This Disease Is Related to 1 DME Molecule(s)

Gene Name	DME ID	Evidence Level	Mode of Inheritance	REF
PNPO	DE3Z1RA	Definitive	Biomarker	[6]

This Disease Is Related to 4 DOT Molecule(s)

Gene Name	DOT ID	Evidence Level	Mode of Inheritance	REF
PLPBP	OT9DZ8P6	Supportive	Autosomal recessive	[5]
SLC13A5	OTPH1TA7	Supportive	Autosomal recessive	[5]
ALDH7A1	OTV57BZD	Definitive	Autosomal recessive	[7]
STXBP1	OTRYA8C3	Definitive	Genetic Variation	[8]

References

• [1] Pyridoxine-Dependent Epilepsy and Antiquitin Deficiency Resulting in Neonatal-Onset Refractory Seizures. Brain Sci. 2021 Dec 31;12(1):65.
• [2] Oxidative Stress and Renal Fibrosis: Recent Insights for the Development of Novel Therapeutic Strategies.Front Physiol. 2018 Feb 16;9:105. doi: 10.3389/fphys.2018.00105. eCollection 2018.
• [3] Glutamate decarboxylase is not genetically linked to pyridoxine-dependent seizures.Neurology. 2000 Jul 25;55(2):309-11. doi: 10.1212/wnl.55.2.309.
• [4] Targeting the paracrine hormone-dependent guanylate cyclase/cGMP/phosphodiesterases signaling pathway for colorectal cancer prevention.Semin Cancer Biol. 2019 Jun;56:168-174. doi: 10.1016/j.semcancer.2018.08.011. Epub 2018 Sep 3.
• [5] Mutations in PROSC Disrupt Cellular Pyridoxal Phosphate Homeostasis and Cause Vitamin-B(6)-Dependent Epilepsy. Am J Hum Genet. 2016 Dec 1;99(6):1325-1337. doi: 10.1016/j.ajhg.2016.10.011.
• [6] Pyridoxine responsiveness in novel mutations of the PNPO gene.Neurology. 2014 Apr 22;82(16):1425-33. doi: 10.1212/WNL.0000000000000344. Epub 2014 Mar 21.
• [7] Technical standards for the interpretation and reporting of constitutional copy-number variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics (ACMG) and the Clinical Genome Resource (ClinGen). Genet Med. 2020 Feb;22(2):245-257. doi: 10.1038/s41436-019-0686-8. Epub 2019 Nov 6.
• [8] Folinic acid responsive epilepsy in Ohtahara syndrome caused by STXBP1 mutation.Pediatr Neurol. 2014 Feb;50(2):177-80. doi: 10.1016/j.pediatrneurol.2013.10.006. Epub 2013 Oct 24.