A Novel SLC25A15 Mmutation Causing Hyperornithinemia-Hyperammonemia-Homocitrullinuria Syndrome
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Hyperornithinemia-hyperammonemia-homocitrullinuria syndrome (HHH syndrome) is a neurometabolic disorder with highly variable clinical severity ranging from mild learning disability to severe encephalopathy. Diagnosis of HHH syndrome can easily be delayed or misdiagnosed due to insidious symptoms and incomplete biochemical findings, in that case, genetic testing should be considered to confirm the diagnosis. HHH syndrome is caused by biallelic mutations of SLC25A15, which is involved in the urea cycle and the ornithine transport into mitochondria. Here we report a boy with spastic paraplegia and asymptomatic younger sister who have compound heterozygous mutations of c.535C>T (p.R179*) and c.116C>A (p.T39K) in the SLC25A15 gene. We identified that p.T39K mutation is a novel pathogenic mutation causing HHH syndrome and that p.R179*, which is prevalent in Japanese and Middle Eastern heritage, is also found in the Korean population.
Abstract
Hyperornithinemia-hyperammonemia-homocitrullinuria syndrome (HHH syndrome) is a neurometabolic disorder with highly variable clinical severity ranging from mild learning disability to severe encephalopathy. Diagnosis of HHH syndrome can easily be delayed or misdiagnosed due to insidious symptoms and incomplete biochemical findings, in that case, genetic testing should be considered to confirm the diagnosis. HHH syndrome is caused by biallelic mutations of SLC25A15, which is involved in the urea cycle and the ornithine transport into mitochondria. Here we report a boy with spastic paraplegia and asymptomatic younger sister who have compound heterozygous mutations of c.535C>T (p.R179*) and c.116C>A (p.T39K) in the SLC25A15 gene. We identified that p.T39K mutation is a novel pathogenic mutation causing HHH syndrome and that p.R179*, which is prevalent in Japanese and Middle Eastern heritage, is also found in the Korean population.
참고문헌 (20)
- Camacho JA, "Hyperornithinaemia-hyperammonaemia-homocitrullinuria syndrome is caused by mutations in a gene encoding a mitochondrial ornithine transporter", Nat Genet, 22, pp.151~158 (1999)
- Dionisi-Vici C, "Inborn errors of metabolism in the Italian pediatric population : a national retrospective survey", J Pediatr, 140, pp.321~327 (2002)
- Summar ML, "The incidence of urea cycle disorders", Mol Genet Metab, 110, pp.179~180 (2013)
- Shih VE, "Neonatal form of the hyperornithinaemia, hyperammonaemia, and homocitrullinuria (HHH) syndrome and prenatal diagnosis", Prenat Diagn, 12, pp.717~723 (1992)
- Al-Hassnan ZN, "Hyperornithinemia-hyperammonemiahomocitrullinuria syndrome with stroke-like imaging presentation:clinical, biochemical and molecular analysis", J Neurol Sci, 264, pp.187~194 (2008)
- Lemay JF, "Hyperammonemia-hyperornithinemia-homocitrullinuria syndrome: neurologic, ophthalmologic, and neuropsychologic examination of six patients", J Pediatr, 121, pp.725~730 (1992)
- Gatfield PD, "Hyperornithinemia, hyperammonemia, and homocitrullinuria associated with decreased carbamyl phosphate synthetase I activity", Pediatr Res, 9, pp.488~497 (1975)
- Debray FG, "Phenotypic variability among patients with hyperornithinaemia-hyperammonaemia-homocitrullinuria syndrome homozygous for the delF188 mutation in SLC25A15", J Med Genet, 45, pp.759~764 (2008)
- Haberle J, "Suggested guidelines for the diagnosis and management of urea cycle disorders", Orphanet J Rare Dis, 7, pp.32~ (2012)
- Martinelli D, "The hyperornithinemia-hyperammonemia-homocitrullinuria syndrome", Orphanet J Rare Dis, 10, pp.29~ (2015)
- Shih VE, "Hyperornithinemia, hyperammonemia, and homocitrullinuria. A new disorder of amino acid metabolism associated with myoclonic seizures and mental retardation", Am J Dis Child, 117, pp.83~92 (1969)
- Palmieri F, "Diseases caused by defects of mitochondrial carriers : a review", Biochim Biophys Acta, 1777, pp.564~578 (2008)
- 황민호, "형제에서 발생된 Hyperonithinemia Htperammonemia Homocitrullimuria(HHH)증후군2례", Korean Journal of Pediatrics, 44(10), pp.1206~1210 (2001), 대한소아과학회
- Camacho JA, "Clinical and functional characterization of a human ORNT1 mutation(T32R)in the hyperornithinemia-hyperammonemia-homocitrullinuria(HHH)syndrome", Pediatr Res, 60, pp.423~429 (2006)
- Sokoro AA, "Diagnosis and high incidence of hyperornithinemia-hyperammonemia-homocitrullinemia (HHH) syndrome in northern Saskatchewan", J Inherit Metab Dis, 33(Suppl 3), pp.S275~S281 (2010)
- Camacho J, "Hyperornithinemia-Hyperammonemia-Homocitrullinuria Syndrome" (1993), GeneReviews(R)
- Tsujino S, "Hyperornithinemia, hyperammonemia and homocitrullinuria--a case report and study of ornithine metabolism using in vivo deuterium labelling", Clin Chim Acta, 201, pp.129~133 (1991)
- Indiveri C, "Identification and purification of the ornithine", citrulline carrier from rat liver mitochondria, 1992, pp.207, 449~454
- Miyamoto T, "Diagnosis of Japanese patients with HHH syndrome by molecular genetic analysis: a common mutation, R179X", J Hum Genet, 46, pp.260~262 (2001)
- Tessa A, "Identification of novel mutations in the SLC25A15 gene in hyperornithinemia-hyperammonemiahomocitrullinuria (HHH) syndrome: a clinical, molecular, and functional study", Hum Mutat, 30, pp.741~748 (2009)