Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0036572 (seizures)
 80,221 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Peroxisome biogenesis disorders result from defects in peroxin proteins involved in peroxisomal matrix and membrane protein import. Peroxins are encoded in peroxin protein genes; to date, the PEX genes responsible for all 12 peroxisome biogenesis disorders complementation groups are known. Peroxin protein 1 deficiency associated with complementation group 1 is responsible for disease in approximately two thirds of all patients with a peroxisome biogenesis disorder. Their phenotypes range from severe to mild, and it appears to be a phenotype-genotype relationship. This case report describes a patient with peroxin protein 1 deficiency presenting as Leber congenital amaurosis, in whom the diagnosis was questioned at the age of 2 years when seizures first appeared and mild facial dysmorphia became evident.
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PMID:PEX1 deficiency presenting as Leber congenital amaurosis. 1530 38

Peroxisomal biogenesis disorders (PBD) are groups of inherited neurometabolic disorders caused by defects in PEX genes. We report on a female infant, born to a consanguineous parents (first degree cousins), who presented with inactivity, poor sucking, and hypotonia early in the neonatal period. She had subtle dysmorphic features. Liver function tests were impaired with raised liver enzymes, conjugated and unconjugated hyperbilirubinemia. CT of the brain showed diffuse bilateral changes. She developed seizures with an abnormal EEG. Plasma very long chain fatty acid analysis showed high C26:0 levels and increasedC26:0/C22:0 and C24:0/C22:0 ratios, which is consistent with a PBD. Studies in fibroblasts including plasmalogen biosynthesis, peroxisomal fatty acid alfa and beta oxidation confirmed the diagnosis of PBD. Immunofluoresence microscopy revealed the absence of peroxisomes in fibroblasts. The patient was assigned to the PEX19 complementation group. Subsequent mutation analysis of the PEX19 gene revealed homozygosity for a c.320delA frameshift mutation. The patient had a stormy course with multiple admissions to the pediatric intensive care unit with pneumonia, liver impairment, sepsis, and epilepsy. At 1 year of age she developed metabolic acidosis with normal anion gap, proteinuria, aminoaciduria, and glucosuria consistent with a renal tubular defect. Abdominal ultrasound showed multiple gallstones. Other causes of gallstones like haemoglobinopathy were excluded. So far, only two siblings had been reported with mutations in the PEX19 gene. Our patient showed a previously unrecognized association of gallstones and a renal tubular defect with a PBD.
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PMID:A mutation in PEX19 causes a severe clinical phenotype in a patient with peroxisomal biogenesis disorder. 2068 89

Zellweger syndrome is a peroxisomal disorder resulting from the mutations in PEX genes generally presenting in the neonatal period with profound hypotonia seizures, inability to feed, liver cysts with hepatic dysfunction, chondrodysplasia punctata. Kabuki make-up syndrome is a multiple congenital anomalies and mental retardation syndrome with characteristic facial appearance, skeletal abnormalities, dermatoglyphic abnormalities, mental retardation and short stature. Abnormal liver functions and some atypical findings were also reported in some patients with Kabuki syndrome. In this report a case with late onset Zellweger syndrome who had some phenotypical findings which are also seen in Kabuki Syndrome will be presented. The inclusion of Zellweger syndrome into the differential diagnosis of the patients with Kabuki-like phenotype in addition to abnormal liver functions is emphasized.
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PMID:An infantile case of Zellweger syndrome presented with Kabuki-like phenotype. 2184 15

Zellweger syndrome (ZS) is the severest variety of peroxisomal biogenesis disorder (PBD). This is a fatal hereditary, autosomal recessive disorder. It is characterized by the absence of peroxisomes in the cells which are essential for many metabolic functions especially beta oxidation of very long chain fatty acids (VLCFAs). We report the case of a female Saudi toddler. She presented with dysmorphism, profound hypotonia, psychomotor retardation, seizures, and loss of hearing and vision with findings of optic atrophy. Biochemical study revealed significantly elevated level of VLCFAs, cerotic acid and phytanic acid. She also had periventricular leukomalacia and abnormal electroencephalography results and a PEX 1 gene mutation. The clinical data and investigations were consistent with ZS. As it is fatal in early life, genetic counseling and prenatal diagnosis are thus crucial.
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PMID:Zellweger syndrome - a lethal peroxisome biogenesis disorder. 2332 10

Zellweger syndrome (ZS) is a severe manifestation of disease within the spectrum of peroxisome biogenesis disorders that includes neonatal adrenoleukodystrophy, infantile Refsum disease, and rhizomelic chondroplasia punctata. Patients with ZS present in the neonatal period with a characteristic phenotype of distinctive facial stigmata, pronounced hypotonia, poor feeding, hepatic dysfunction, and often seizures and boney abnormalities. In patients with ZS, a mutation in one of the PEX genes coding for a peroxin (a peroxisome assembly protein) creates functionally incompetent organelles causing an accumulation of very long chain fatty acids (VLCFA), among other complications. Despite an absence of treatment options, prompt diagnosis of ZS is important for providing appropriate symptomatic care, definitive genetic testing, and counseling regarding family planning.
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PMID:Child neurology: Zellweger syndrome. 2367 47

Peroxisome biogenesis disorders (PBDs) represent a spectrum of human genetic disorders that are characterized by damaged peroxisome assembly. In the newborn period, the characteristics of affected patients include dysmorphic facial features, neonatal hypotonia, seizures, ocular abnormalities, poor feeding, liver cysts with hepatic dysfunction and skeletal defects. These can be caused by a defect in at least 14 different PEX genes. In this study, whole-exome sequencing (WES) was performed on samples from two Chinese newborns with clinical features of Zellweger syndrome. WES identified two novel mutations (c.2416+1G>T and c.2489delT) in patient 1 and another two novel mutations (c.1483+1G>A and c.1727dupG) in patient 2 in the PEX1 gene. All four mutations have a serious influence on the protein function, which also highlights the power of WES, particularly in clinically challenging cases.
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PMID:Novel compound heterozygous mutations in the PEX1 gene in two Chinese newborns with Zellweger syndrome based on whole exome sequencing. 2843 12

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.
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PMID:Two different missense mutations of PEX genes in two similar patients with severe Zellweger syndrome: an argument on the genotype-phenotype correlation. 3206 32