Peroxisome Biogenesis Disorder 12A (Zellweger)

Alternative Names

  • Peroxisome Biogenesis Disorder, Complementation Group 14
  • CG14
  • Peroxisome Biogenesis Disorder, Complentation group J
  • CGJ
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WHO-ICD-10 version:2010

Congenital malformations, deformations and chromosomal abnormalities

Other congenital malformations

OMIM Number

614886

Mode of Inheritance

Autosomal recessive

Gene Map Locus

1q23.2

Description

Zellweger syndrome (ZS) comprises of 14 complementation groups; these constitute the most common and most severe phenotypic class of Peroxisome Biogenesis Disorders (PBD).  PBD12A is a subtype of ZS that is caused by PEX19 dysfunction.  The absence of peroxisomes impairs catabolism and detoxification of various compounds, as well as plasmalogen biosynthesis.  Reported clinical features of PBD12A include neonatal hypotonia, poor growth development, CNS and skeletal abnormalities, epilepsy, hydrocephaly, genital abnormalities, and subtle dysmorphic features (including cranial and ear asymmetry, low hairline, triangular face, widely open anterior and posterior fontanelles, and broad nasal bridge).  Other anomalies include hyperbilirubenia and elevated liver activity.

Diagnosis of PBD is mainly determined by serum measurement of very long chain fatty acids (VLCFA), plasmalogen, as well as phytanic and pristanic acid levels; deficient oxidation activity leads to abnormally increased VLCFA, phytanic, and pristanic acid levels, and decreased plasmalogen levels.  Immunofluorescence of patient cells is used to confirm absence of peroxisomes. Complementation testing of PBD related genes (peroxins) can identify the candidate gene for mutation analysis.  Therapy is currently focused on management of the involved symptoms. 

Molecular Genetics

PBD12A is an autosomal recessive disorder caused by homozygous mutations in PEX19.  PEX19 encodes a cytosolic protein involved in peroxisome membrane assembly and preservation.  It functions as a chaperone and peroxisome import receptor of class I peroxisomal membrane proteins (PMP).  With only a few cases identified, PEX19 deficiency is thought to represent <1% of the zellweger syndrome spectrum which has an estimated incidence of 1:50,000 cases. 

Epidemiology in the Arab World

View Map
Subject IDCountrySexFamily HistoryParental ConsanguinityHPO TermsVariantZygosityMode of InheritanceReferenceRemarks
614886.1.1Saudi ArabiaFemaleNoYes Hypotonia; Global developmental delay; C...NM_002857.4:c.320delHomozygousAutosomal, RecessiveMohamed et al. 2010 Patient died at 16 m...
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