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)

Hyperornithinemia, hyperammonemia, and homocitrullinuria (HHH) syndrome is caused by mutations in the SLC25A15 (ORNT1) gene encoding the mitochondrial ornithine transporter, but the mechanism of pathogenesis of the encephalopathy, spastic paraparesis and hepatopathy remains undetermined. HHH syndrome was diagnosed in a 2-year-old Palestinian boy with developmental delay and seizures, and subsequently in his 13-year-old brother with developmental delay. Direct sequencing of the PCR products of SLC25A15 exon amplifications revealed that both brothers were homozygous for a novel 446G deletion in exon 3 as well as for a 760A>T (I254L) polymorphism in exon 5, which is downstream of a premature termination codon produced by the frameshift resulting from the 446G deletion. The index patient had elevated liver enzymes as well as hyperalaninemia, lactic acidemia with an elevated lactate to pyruvate ratio, and increased urinary excretion of lactate, glutarate and Krebs cycle intermediates. These findings are indicative of mitochondrial dysfunction and are in accordance with ultrastructural studies showing increased numbers of large and bizarre mitochondria in liver, muscle, leukocytes and fibroblasts of some HHH patients. Neurologic and hepatic manifestations are characteristic of some primary mitochondrial disorders. Secondary mitochondrial dysfunction may contribute to the pathogenesis of these same features in HHH syndrome.
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PMID:Hyperornithinemia, hyperammonemia, and homocitrullinuria syndrome with evidence of mitochondrial dysfunction due to a novel SLC25A15 (ORNT1) gene mutation in a Palestinian family. 1475 33

The hyperornithinemia-hyperammonemia-homocitrullinuria (HHH) syndrome (MIM 238970) is an autosomal recessive metabolic disorder caused by a deficiency of the mitochondrial ornithine transporter, one of the urea cycle components. Mutations in the SLC25A15 gene have been coupled to the HHH syndrome. We describe a Japanese female patient with the HHH syndrome due to a novel homozygous R275X SLC25A15 mutation and male sibling who presumably carried the same mutation. He exhibited slowly progressive deterioration with seizures, a gait disturbance due to polyneuropathy, episodic confusion, and died of acute encephalopathy at 34 years of age while the proband exhibited moderate mental retardation, seizures, mild spastic paraplegia, and deafness without neurological deterioration for more than 20 years. The clinical features of previously documented patients with the homozygous SLC25A15 mutation demonstrated that genotype did not simply correlate with clinical severity. The phenotypic variability might depend on other factors, such as dietary and other genetic ones.
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PMID:A novel R275X mutation of the SLC25A15 gene in a Japanese patient with the HHH syndrome. 1637 11