Two different missense mutations of PEX genes in two similar patients with severe Zellweger syndrome: an argument on the genotype-phenotype correlation.

Background Peroxisomal biogenesis disorders (PBDs) include a miscellaneous group of diseases which cause serious multisystem disease. Mutations of 13 different PEX genes lead to PBDs including Zellweger syndrome (ZS). Different types of mutations of PEX1 and PEX10 genes are correlated with broad-range phenotypes of PBDs. Case presentation Patient 1 is a 4-month-old boy who was affected by myoclonic seizures, poor oral feeding since birth. The patient was hypotonic and had hepatosplenomegaly. Patient 2 is a 2-month-old boy who presented with decreased movement, severe hypotonia and failure to thrive. The laboratory studies of the patients revealed increased plasma very-long-chain fatty acids (VLCFAs). The genetic analyses of patient 1 demonstrated the first homozygous missense mutation in the PEX10 gene. A novel homozygous missense mutation was found in the PEX1 gene in patient 2. Conclusions This report highlights that the detected homozygous missense mutations of PEX10 and PEX1 genes and the substitutions of specific amino acids lead to the severe form of PBDs.

Scimitar-like ossification of patellae led to diagnosis of Zellweger syndrome in newborn: a case report.

Zellweger syndrome is the most severe form of a group of autosomal recessive disorders with defective peroxisomes. We report a case of Zellweger syndrome in a newborn baby, which was first suspected by the presence of scimitar-like patella seen on skeletal survey. The subsequent brain MRI showed germinolytic cysts and polymicrogyria, which furthered the suspicion. Laboratory and genetic results confirmed the diagnosis. To date, there are a limited number of case reports of this rare disease. We emphasize skeletal findings that can lead to targeted genetic and laboratory testing and hence earlier diagnosis.

Zellweger syndrome: Depiction of MRI findings in early infancy at 3.0 Tesla.

Zellweger syndrome, also referred to as cerebrohepatorenal syndrome, is a rare autosomal recessive disease representing the most severe form of the peroxisomal biogenesis disorders. Neuroanatomical sequelae include impaired neuronal migration, diffuse hypomyelination, and sensorineural degeneration. Due to the rare and severe nature of this disorder, early mortality, and comorbidities that place the patient at risk for sedated imaging, high-resolution magnetic resonance imaging findings of Zellweger syndrome are scarce in the literature. Presented here is a case of this rare disease imaged at 3.0 Tesla.

Fetal echogenic bowel in association with Zellweger syndrome.

Increased echogenicity of fetal bowel in the second trimester obstetrical ultrasound has been described in association with several pathologic conditions, such as growth restriction, aneuploidy, cystic fibrosis, congenital infections, and gastrointestinal malformations. Zellweger syndrome (ZS) is the prototype of peroxisomal disorders characterized by craniofacial dysmorphism and severe neurologic abnormalities. We report two cases with fetal echogenic bowel (FEB) but no associated anomalies and normal fetal growth. After birth, clinical and laboratory findings led to diagnosis of ZS. Association of FEB with neurometabolic disorders is limited to a few case reports in the medical literature. To the best of our knowledge, this is the first report of ZS associated with FEB.

First-trimester increased nuchal translucency and fetal hypokinesia associated with Zellweger syndrome.

We report the prenatal detection of increased nuchal translucency and decreased fetal movements, at 11 weeks of gestation, in a fetus at risk for Zellweger syndrome. The diagnosis of Zellweger syndrome was confirmed by metabolic studies on cultured chorionic villus sampling (CVS) cells and the pregnancy was terminated. The couple's subsequent pregnancy was monitored using the same method. In this pregnancy the nuchal translucency measured at 12 weeks' gestation was normal, the fetus was active, and biochemical studies using CVS and amniocentesis confirmed normal results. We believe this to be the first reported case of Zellweger syndrome followed prenatally in which an increased nuchal translucency and fetal hypokinesia were detected in the first trimester. During the pregnancy with the affected child the maternal serum screen (MSS) showed low estriol level. We believe this to be the second report of a low estriol level on MSS in a pregnancy affected with Zellweger syndrome.

Enlarged nuchal translucency and low serum protein concentrations as possible markers for Zellweger syndrome.

We present a case of a fetus in which an enlarged nuchal translucency was detected at 12 weeks' gestation. The karyotype was normal. Subsequent ultrasound examination showed no obvious fetal abnormalities apart from a mild pericardial effusion. Serum screening revealed very low concentrations of estriol and human chorionic gonadotropin. After birth the diagnosis of Zellweger syndrome was made. Nuchal translucency screening, estriol level identification and detailed ultrasound scanning may help to identify fetuses affected by this syndrome.

MRI findings of Zellweger syndrome.

A patient with Zellweger syndrome, who manifested marked dilatation of the lateral ventricles, observed at 34 weeks gestation by fetal ultrasonography, is reported. Postnatal magnetic resonance imaging revealed marked colpocephaly and hypogenesis of the posterior part of the corpus callosum. However, pachygyria was limited to the perisylvian regions. Biochemical diagnosis was based on increased serum very-long-chain fatty acids, 2-hydroxysebacic aciduria, and the detection of the ghosts of peroxisomal membrane in cultured fibroblasts. The patient was classified as belonging to group B of this syndrome by complementation study.

Subependymal germinolytic cysts in Zellweger syndrome.

Ultrasonographic demonstration of periventricular cysts is usually associated with cystic periventricular leucomalacia due to necrosis of periventricular unmyelinated white matter. Cystic spaces with a similar appearance may also arise from prenatal lysis of fetal periventricular matrix tissue, rather than immature white matter. The resultant empty spaces are called "pseudocysts" or germinolytic cysts. Neuropathological studies have shown that germinolytic cysts may arise in Zellweger syndrome (generalized peroxisomal disorder). Here, we report their ultrasonographic demonstration in Zellweger syndrome, emphasizing the potential value of this sign in the diagnosis.

Punctate epiphyses: a radiological sign not a disease.

Punctate epiphyses are caused by a diverse group of conditions. They may be an inherited part of certain bone dysplasias or an incidental finding occurring occasionally in various disorders. The pattern of the puncta together with other radiologic findings aid in making the correct diagnosis.

A case of pseudo-Zellweger syndrome with a possible bifunctional enzyme deficiency but detectable enzyme protein. Comparison of two cases of Zellweger syndrome.

Three infants with peroxisomal disorders were investigated clinicobiochemically and neuroradiologically. Two had classical Zellweger syndrome, and cranial CT scans showed typical disproportionate enlargement of the occipital horns of the lateral ventricles (colpocephaly) with marked hypodensity of the white matter. In one female infant, although the clinical findings were similar to those in Zellweger syndrome, some findings, such as elevated transaminase levels, liver fibrosis, the absence of renal cortical cysts and colpocephaly, were negative or milder. Biochemical analyses revealed increased very long-chain fatty acids, dicarboxylic aciduria and impaired beta-oxidation of lignoceric acid. However, peroxisomes were abundantly present in hepatocytes and cultured fibroblasts, and all peroxisomal beta-oxidation enzyme proteins were detected on immunoblot analysis. A cell fusion study suggested that the enzyme responsible for this case of 'pseudo-Zellweger syndrome' is bifunctional.