Zellweger syndrome (ZS) is an autosomal recessive multiple congenital anomaly syndrome resulting from disordered peroxisome biogenesis. Affected children present in the newborn period with profound hypotonia, seizures, and inability to feed. Characteristic craniofacial anomalies, eye abnormalities, neuronal migration ... Zellweger syndrome (ZS) is an autosomal recessive multiple congenital anomaly syndrome resulting from disordered peroxisome biogenesis. Affected children present in the newborn period with profound hypotonia, seizures, and inability to feed. Characteristic craniofacial anomalies, eye abnormalities, neuronal migration defects, hepatomegaly, and chondrodysplasia punctata are present. Children with this condition do not show any significant development and usually die in the first year of life (summary by Steinberg et al., 2006). For a complete phenotypic description and a discussion of genetic heterogeneity of Zellweger syndrome, see 214100. Individuals with PBDs of complementation group K (CGK) have mutations in the PEX14 gene. For information on the history of PBD complementation groups, see 214100.
Shimozawa et al. (2004) studied a patient with Zellweger syndrome. At birth the patient showed typical craniofacial dysmorphia of Zellweger syndrome, including large open fontanels, high forehead, flat occiput, low/broad nasal bridge, and micrognathia, as well as neurologic ... Shimozawa et al. (2004) studied a patient with Zellweger syndrome. At birth the patient showed typical craniofacial dysmorphia of Zellweger syndrome, including large open fontanels, high forehead, flat occiput, low/broad nasal bridge, and micrognathia, as well as neurologic abnormalities including hypotonia. Plasma analysis showed elevated very long chain fatty acids (VLCFA) and di- and trihydroxycholestanoic acid, and a normal phytanic acid level. Erythrocyte plasmalogens were undetectable. The patient died at 10 days of age. The Pakistani patient with Zellweger syndrome studied by Huybrechts et al. (2008) showed prolonged neonatal hyperbilirubinemia and presented at 3 months of age with icterus, axial hypotonia, and hepatomegaly. Dysmorphic features included slight dolichocephaly, triangular face, and large fontanel. Metabolic screening showed increased long chain fatty acids and hypoketotic dicarboxylic aciduria. Further studies showed severe hepatic parenchymatic destruction and cholestasis. His gaze fixed and followed normally, he had normal spontaneous movements in all limbs, but deep tendon reflexes were absent. Radiologic examination of the skeleton was normal. Ophthalmologic examination showed posterior embryotoxon. Metabolic screening at this age showed normal plasma amino acids, phytanic acid, pristanic acid, and C24:0 levels; increased C26:0 values, and decreased C22:0 and plasmalogen concentrations. Cerebral ultrasound and electroencephalography were normal, but brain magnetic resonance imaging (MRI) at 5 months and computed tomography (CT) at 13 months showed a polymicrogyria in the right frontal and parietal cortex and left Rolandic cortex, and bilateral zones of laminar heterotopia. An epileptic seizure (unresponsive, cyanosis) was suspected at age 13 months. At the age of 21 months, the patient had lost vision and showed generalized hypotonia, with no spontaneous movements anymore. The cholestasis had completely disappeared (normal bilirubin and alkaline phosphatase) but transaminases remained high. Plasma phytanic acid was at the upper limit of normal, and pristanic acid increased from the age of 14 months on. Plasmalogen content of erythrocytes remained low. Family history revealed that the mother had a mentally retarded sib and a sister with 3 children who all died before age 1 year.
The patient with Zellweger syndrome studied by Shimozawa et al. (2004) carried a homozygous nonsense mutation in the PEX14 gene (601791.0001).
Huybrechts et al. (2008) detected a 41-kb deletion in the PEX14 gene (601791.0002) in a ... The patient with Zellweger syndrome studied by Shimozawa et al. (2004) carried a homozygous nonsense mutation in the PEX14 gene (601791.0001). Huybrechts et al. (2008) detected a 41-kb deletion in the PEX14 gene (601791.0002) in a patient with Zellweger syndrome.