Details of Disease

General Information of Disease (ID: DISU4RVU)

• Disease Name: Mitochondrial DNA depletion syndrome 4a
• Synonyms: Alpers diffuse Degeneration of cerebral Gray matter with hepatic cirrhosis; neuronal Degeneration of childhood with liver disease, progressive; Poliodystrophia cerebri progressiva; Alpers diffuse Degeneration of cerebral Grey matter with hepatic cirrhosis; infantile poliodystrophy; PNDC; progressive cerebral poliodystrophy; MTDPS4A; diffuse cerebral degeneration in infancy; mitochondrial DNA depletion syndrome 4A (Alpers type); Alpers Disease; mitochondrial DNA depletion syndrome type 4a; AHS; Alpers-Huttenlocher syndrome; Alpers Huttenlocher syndrome; Alpers disease; AHD; progressive neuronal degeneration of childhood with liver disease; Alpers progressive infantile poliodystrophy; Alpers Huttenlocher disease; mitochondrial DNA depletion syndrome 4A; Alpers' disease or gray-matter degeneration; Alper's syndrome; progressive sclerosing poliodystrophy; Alpers progressive sclerosing poliodystrophy; Alpers syndrome; Alper syndrome; Alper's disease
• Definition: Alpers Huttenlocher syndrome (AHS) is a cerebrohepatopathy and a rare and severe form of mitochondrial DNA (mtDNA) depletion syndrome characterized by the triad of progressive developmental regression, intractable seizures, and hepatic failure.
• Disease Hierarchy:
  DISOEVKS: Metabolic epilepsy
  DISSYRHC: Hereditary peripheral neuropathy
  DIS6SVEE: Syndromic disease
  DISPN7D2: Inherited neurodegenerative disorder
  DISXOJLH: Mitochondrial DNA depletion syndrome, hepatocerebral form
  DISU4RVU: Mitochondrial DNA depletion syndrome 4a
• Disease Identifiers:
  MONDO ID: MONDO_0008758
  MESH ID: D002549
  UMLS CUI: C0205710
  OMIM ID: 203700
  MedGen ID: 60012
  Orphanet ID: 726
  SNOMED CT ID: 20415001

Molecular Interaction Atlas (MIA) of This Disease

This Disease Is Related to 3 DTT Molecule(s)

Gene Name	DTT ID	Evidence Level	Mode of Inheritance	REF
NPTX2	TTNJ5A6	moderate	Genetic Variation	[1]
ABL2	TT1A6HL	Strong	Genetic Variation	[2]
AHSG	TTKF4WV	Strong	Biomarker	[3]

This Disease Is Related to 1 DME Molecule(s)

Gene Name	DME ID	Evidence Level	Mode of Inheritance	REF
FARS2	DE0WGR8	Strong	Genetic Variation	[4]

This Disease Is Related to 10 DOT Molecule(s)

Gene Name	DOT ID	Evidence Level	Mode of Inheritance	REF
DARS2	OTVPFTBG	moderate	Biomarker	[1]
CARS1	OTOUZF6O	Strong	Genetic Variation	[5]
DGUOK	OT78HUZB	Strong	Genetic Variation	[6]
MPV17	OT579DMU	Strong	Genetic Variation	[7]
NARS2	OTL5X535	Strong	Genetic Variation	[8]
OSR1	OTB19LEQ	Strong	Biomarker	[9]
PARS2	OTMBBH7K	Strong	Genetic Variation	[10]
RERE	OT3G4GBZ	Strong	Genetic Variation	[2]
SNCB	OTELSEK6	Strong	Biomarker	[11]
POLG	OTDUCT04	Definitive	Autosomal recessive	[12]

References

• [1] Epilepsy in mitochondrial disorders.Seizure. 2012 Jun;21(5):316-21. doi: 10.1016/j.seizure.2012.03.003. Epub 2012 Mar 27.
• [2] Functional and morphological abnormalities of mitochondria in human cells containing mitochondrial DNA with pathogenic point mutations in tRNA genes.J Biol Chem. 1994 Jul 22;269(29):19060-6.
• [3] Myoclonus epilepsy in mitochondrial disorders.Epileptic Disord. 2016 Sep 1;18(S2):94-102. doi: 10.1684/epd.2016.0846.
• [4] Mitochondrial phenylalanyl-tRNA synthetase mutations underlie fatal infantile Alpers encephalopathy.Hum Mol Genet. 2012 Oct 15;21(20):4521-9. doi: 10.1093/hmg/dds294. Epub 2012 Jul 23.
• [5] Clinicopathologic Findings of CARS2 Mutation.Pediatr Neurol. 2018 Oct;87:65-69. doi: 10.1016/j.pediatrneurol.2018.06.009. Epub 2018 Jul 4.
• [6] Mitochondrial DNA depletion is a prevalent cause of multiple respiratory chain deficiency in childhood.J Pediatr. 2007 May;150(5):531-4, 534.e1-6. doi: 10.1016/j.jpeds.2007.01.044.
• [7] Mitochondrial syndromes with leukoencephalopathies.Semin Neurol. 2012 Feb;32(1):55-61. doi: 10.1055/s-0032-1306387. Epub 2012 Mar 15.
• [8] PARS2 and NARS2 mutations in infantile-onset neurodegenerative disorder.J Hum Genet. 2017 Apr;62(5):525-529. doi: 10.1038/jhg.2016.163. Epub 2017 Jan 12.
• [9] Child and adolescent traumatic brain injury: correlates of disruptive behaviour disorders.Brain Inj. 1998 Jan;12(1):41-52. doi: 10.1080/026990598122845.
• [10] The genotypic and phenotypic spectrum of PARS2-related infantile-onset encephalopathy. J Hum Genet. 2018 Sep;63(9):971-980. doi: 10.1038/s10038-018-0478-z. Epub 2018 Jun 18.
• [11] -Synuclein-reactive T cells induce autoimmune CNS grey matter degeneration.Nature. 2019 Feb;566(7745):503-508. doi: 10.1038/s41586-019-0964-2. Epub 2019 Feb 20.
• [12] Flexible and scalable diagnostic filtering of genomic variants using G2P with Ensembl VEP. Nat Commun. 2019 May 30;10(1):2373. doi: 10.1038/s41467-019-10016-3.