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


Mode of Inheritance

Autosomal recessive

Gene Map Locus



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

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Other Reports

Saudi Arabia

Mohamed et al., (2010) reported on a Saudi infant diagnosed with peroxisome biogenesis disorder 12A (PBD12A).  She was firstborn to consanguineous (first-cousin) asymptomatic parents.  The infant presented with hypotonia, lethargy, growth parameters at the 3rd centile, and global developmental delay.  Dysmorphic features included cranial asymmetry, abnormal asymmetric ears, low hairline, triangular face, prominent nose and broad nasal bridge, receding chin, scaphocephaly, open anterior and posterior fontanelles, epicanthic folds, and periorbital swelling.  MRI revealed cerebral atrophy and diffuse demylination. She exhibited hyperbilirubinemia, elevated liver enzyme activity.  The clinical course followed with dehydration, pneumonia, bronchiolitis, liver impairment, sepsis, and gall stones; she developed a renal tubular defect with metabolic acidosis, proteinuria, aminoaciduria, and glucosuria.  At 16 months of age, she succumbed to sepsis, coagulopathy, and liver failure. Biochemical analysis of very long fatty acid chains and dihydroxyacetone-phosphate acyltransferase (DHAPAT) in patient fibroblasts revealed abnormally high C26:0 (0.94 µmol/g protein), C26:0/C22:0 (0.27), and C24:0/C22:0 (2.54) levels, as well as negligible DHAPAT activity (0.6nmol/mg/2hr).  Phytanic and pristanic acid oxidation was impaired in patient fibroblasts, however levels were not found increased in plasma.  An absence of patient fibroblast peroxisomes was subsequently determined; this lead to complementation testing of possible dysfunctional peroxins, which narrowed the search to PEX19.  Mutation analysis revealed a c.320delA deletion resulting in the frameshift mutation p.K107SfsX13.

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