1Department of Laboratory Medicine and Genetics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
2Department of Pediatrics, Soonchunhyang University College of Medicine, Seoul, Korea
3Department of Laboratory Medicine, Soonchunhyang University Hospital and Soonchunhyang University College of Medicine, Seoul, Korea
4Department of Laboratory Medicine and Genetics, Soonchunhyang University Bucheon Hospital and Soonchunhyang University College of Medicine, Bucheon, Korea
Corresponding authors: Yong-Wha Lee, MD, PhD, Department of Laboratory Medicine and Genetics, Soonchunhyang University Bucheon Hospital and Soonchunhyang University College of Medicine, 1174 Jung-dong, Wonmi-gu, Bucheon, 420-767, Korea Phone: +82-32-621-5943, Fax: +82-32-621-5944,
Chang-Seok Ki, MD, PhD, Department of Laboratory Medicine and Genetics, Samsung Medical Center, Sungkyunkwan University School of Medicine, 50 Irwon-Dong, Gangnam-Gu, Seoul, 135-710, Korea Phone: +82-2-3410-2709, Fax: +82-2-3410-2710,
Citation Information. Clinical Chemistry and Laboratory Medicine. Volume 47, Issue 8, Pages 930–933, ISSN (Online) 1437-4331, ISSN (Print) 1434-6621, DOI: 10.1515/CCLM.2009.223, Available online: 02/07/2009, August 2009
Publication History: Received: 8/3/2009; accepted: 18/5/2009; published online: 02/07/2009
Abstract
Background: Hereditary tyrosinemia type 1 (HT1; MIM 276700) is caused by mutations in the fumarylaceto-acetate hydrolase (FAH) gene, and is the most severe disorder associated with the tyrosine catabolic pathway. HT1 is a very rare disorder and no genetically confirmed case of HT1 in Korea has yet been reported. In this study, we present a Korean neonate with clinical and biochemical features of HT1.
Methods: A female neonate was admitted to our hospital for further work-up of an abnormal newborn screening test. We analyzed amino acids and organic acids in the patient's blood and urine. To confirm the presence of the genetic abnormality, all the coding exons of the FAH gene and the flanking introns were amplified by polymerase chain reaction (PCR).
Results: The patient's newborn screening test revealed increased concentrations of methionine and tyrosine. Subsequent urine organic acid analysis showed increased urinary excretion of 4-hydroxyphenyllactate, 4-hydroxyphenylpyruvate, succinate, and succinylacetone. Gap-PCR and sequence analysis of the FAH gene revealed a homozygous large deletion mutation encompassing exons 12–14. The patient's parents were not consanguineous but were heterozygous carriers of the same mutation.
Conclusions: The patient had a novel, large deletion mutation of FAH and is the first report of genetically confirmed HT1 in Korea.
Clin Chem Lab Med 2009;47:930–3.
Keywords fumarylacetoacetate hydrolase (FAH), Korean, large deletion, novel mutation, tyrosinemia
