Details of Disease

General Information of Disease (ID: DISW52CE)

• Disease Name: Zellweger spectrum disorders
• Synonyms: Zellweger leukodystrophy; ZWS; cerebrohepatorenal syndrome; Zellweger syndrome; congenital iron overload; Zellweger spectrum disorders; ZS
• Definition: The most severe variant seen in the peroxisome biogenesis disorders that is characterized by neuronal migration defects in the brain, dysmorphic craniofacial features, profound hypotonia, neonatal seizures, and liver dysfunction.|Curator note: this refers to the severe form of Zellweger spectrum, see https://github.com/monarch-initiative/mondo-build/issues/61
• Disease Hierarchy:
  DISMFQKM: Developmental anomaly of metabolic origin
  DISBQ6QJ: Peroxisome biogenesis disorder
  DISW52CE: Zellweger spectrum disorders
• Disease Identifiers:
  MONDO ID: MONDO_0019609
  MESH ID: D015211
  UMLS CUI: C0043459
  MedGen ID: 21958
  Orphanet ID: 912
  SNOMED CT ID: 88469006

Molecular Interaction Atlas (MIA) of This Disease

This Disease Is Related to 2 DTT Molecule(s)

Gene Name	DTT ID	Evidence Level	Mode of Inheritance	REF
GPD1	TTKTEAH	Strong	Biomarker	[1]
HSD17B4	TTL1WGS	Strong	Genetic Variation	[2]

This Disease Is Related to 3 DTP Molecule(s)

Gene Name	DTP ID	Evidence Level	Mode of Inheritance	REF
ABCD1	DTKM9DZ	Limited	Biomarker	[3]
ABCD3	DTGLZO4	moderate	Genetic Variation	[4]
ABCD2	DT4MBHD	Strong	Biomarker	[4]

This Disease Is Related to 1 DME Molecule(s)

Gene Name	DME ID	Evidence Level	Mode of Inheritance	REF
HSD17B7	DEDMWFX	Strong	Biomarker	[5]

This Disease Is Related to 23 DOT Molecule(s)

Gene Name	DOT ID	Evidence Level	Mode of Inheritance	REF
GNPAT	OTF6LWPO	Limited	Biomarker	[6]
PAF1	OTDDGUBQ	Limited	Biomarker	[7]
PEX11A	OT8MJ9CJ	Limited	Biomarker	[8]
PEX1	OTQJF0V7	Supportive	Autosomal recessive	[9]
PEX10	OTOCZCFA	Supportive	Autosomal recessive	[9]
PEX11B	OTB1AWPM	Supportive	Autosomal recessive	[10]
PEX12	OT9F6LPN	Supportive	Autosomal recessive	[9]
PEX13	OTXUAYEW	Supportive	Autosomal recessive	[9]
PEX14	OT98BZHE	Supportive	Autosomal recessive	[9]
PEX16	OTJQJ2TZ	Supportive	Autosomal recessive	[9]
PEX19	OTQIDE9Z	Supportive	Autosomal recessive	[9]
PEX2	OTKOEYRM	Supportive	Autosomal recessive	[9]
PEX26	OT5AM0BM	Supportive	Autosomal recessive	[9]
PEX3	OTGZ7ME2	Supportive	Autosomal recessive	[9]
PEX5	OTK4LMG7	Supportive	Autosomal recessive	[9]
PEX6	OTFAK5EF	Supportive	Autosomal recessive	[9]
ABITRAM	OTK1K7BP	Strong	Biomarker	[11]
ACOX2	OT3VH359	Strong	Biomarker	[12]
AGPS	OTFBFPV4	Strong	Biomarker	[6]
BCAP31	OTKSACR4	Strong	Biomarker	[3]
DBI	OT884QY9	Strong	Biomarker	[13]
PEX7	OTM7VBRC	Strong	Biomarker	[14]
PHEX	OTG7N3J7	Strong	Genetic Variation	[15]

References

• [1] Complementation analysis in patients with the clinical phenotype of a generalised peroxisomal disorder.J Med Genet. 1996 Apr;33(4):295-9. doi: 10.1136/jmg.33.4.295.
• [2] Very-long-chain polyunsaturated fatty acids accumulate in phosphatidylcholine of fibroblasts from patients with Zellweger syndrome and acyl-CoA oxidase1 deficiency.Biochim Biophys Acta. 2014 Apr 4;1841(4):610-9. doi: 10.1016/j.bbalip.2014.01.001. Epub 2014 Jan 10.
• [3] Contiguous ABCD1 DXS1357E deletion syndrome: report of an autopsy case.Neuropathology. 2013 Jun;33(3):292-8. doi: 10.1111/j.1440-1789.2012.01348.x. Epub 2012 Sep 21.
• [4] A close relative of the adrenoleukodystrophy (ALD) gene codes for a peroxisomal protein with a specific expression pattern.Proc Natl Acad Sci U S A. 1996 Feb 6;93(3):1265-9. doi: 10.1073/pnas.93.3.1265.
• [5] Unique multifunctional HSD17B4 gene product: 17beta-hydroxysteroid dehydrogenase 4 and D-3-hydroxyacyl-coenzyme A dehydrogenase/hydratase involved in Zellweger syndrome.J Mol Endocrinol. 1999 Jun;22(3):227-40. doi: 10.1677/jme.0.0220227.
• [6] Neonatal punctate calcifications associated with maternal mixed connective tissue disorder (MCTD).BMJ Case Rep. 2018 Oct 12;2018:bcr2017223373. doi: 10.1136/bcr-2017-223373.
• [7] A nonmammalian homolog of the PAF1 gene (Zellweger syndrome) discovered as a gene involved in caryogamy in the fungus Podospora anserina.Cell. 1995 Jun 30;81(7):1043-51. doi: 10.1016/s0092-8674(05)80009-1.
• [8] Peroxisomes in cardiomyocytes and the peroxisome / peroxisome proliferator-activated receptor-loop.Thromb Haemost. 2015 Mar;113(3):452-63. doi: 10.1160/TH14-06-0497. Epub 2015 Jan 22.
• [9] Zellweger Spectrum Disorder. 2003 Dec 12 [updated 2020 Oct 29]. In: Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE, Bean LJH, Gripp KW, Amemiya A, editors. GeneReviews(?) [Internet]. Seattle (WA): University of Washington, Seattle; 1993C2024.
• [10] A novel defect of peroxisome division due to a homozygous non-sense mutation in the PEX11 gene. J Med Genet. 2012 May;49(5):307-13. doi: 10.1136/jmedgenet-2012-100778.
• [11] Newly identified Chinese hamster ovary cell mutants defective in peroxisome assembly represent complementation group A of human peroxisome biogenesis disorders and one novel group in mammals.Exp Cell Res. 1999 May 1;248(2):482-8. doi: 10.1006/excr.1999.4412.
• [12] Molecular characterization of the human peroxisomal branched-chain acyl-CoA oxidase: cDNA cloning, chromosomal assignment, tissue distribution, and evidence for the absence of the protein in Zellweger syndrome.Proc Natl Acad Sci U S A. 1996 Nov 26;93(24):13748-53. doi: 10.1073/pnas.93.24.13748.
• [13] Pathogenesis of peroxisomal deficiency disorders (Zellweger syndrome) may be mediated by misregulation of the GABAergic system via the diazepam binding inhibitor.BMC Pediatr. 2004 Mar 12;4:5. doi: 10.1186/1471-2431-4-5.
• [14] Genotype-phenotype correlations in disorders of peroxisome biogenesis.Mol Genet Metab. 1999 Oct;68(2):316-27. doi: 10.1006/mgme.1999.2926.
• [15] Biochemical and clinical profiles of 52 Tunisian patients affected by Zellweger syndrome.Pediatr Neonatol. 2017 Dec;58(6):484-489. doi: 10.1016/j.pedneo.2016.08.011. Epub 2017 Feb 17.