Clinical, biochemical, and genetic analysis of a Korean neonate with hereditary tyrosinemia type 1

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.