title: Biochemical and molecular diagnosis of tyrosinemia type I with two novel FAH mutations in a Hong Kong chinese patient: recommendation for expanded newborn screening in Hong Kong.
abstract: OBJECTIVE
  Tyrosinemia type I is an autosomal recessive disorder in tyrosine metabolism. In areas without expanded newborn screening, patients present with acute hepatorenal failure in early infancy. Diagnosis can be elusive when clinical presentation is non-specific and biochemical abnormalities are masked by secondary changes. This is the first Hong Kong Chinese report.
  
  
  METHODS
  A two-month-old Chinese male infant with unremarkable antenatal and postnatal history presented with progressive abdominal distension for three days. He suffered from end-stage liver failure, hypoglycemia and hepatic encephalopathy. Diagnostic work-up was complicated starting from rule-out sepsis, intestinal obstruction, volvulus, peritonitis, septic ileus, poisoning to metabolic diseases. Clinical, biochemical and genetic data was described.
  
  
  RESULTS
  The patient showed increases in multiple plasma amino acids including tyrosine, phenylalanine and methionine, and hyper-excretions of 4-hydroxyphenyl-acetate, -pyruvate, and -lactate, as well as N-acetyltyrosine which could be seen in liver failure due to both tyrosinemia type I and non-metabolic conditions. Because of the volatile nature, succinylacetone was almost undetectable. The diagnosis was confirmed by genetic analysis of FAH with two novel mutations, viz. NM_000137.2:c.1063-1G>A and NM_000137.2:c.1035_1037del. Living-related liver transplantation was done. However, the patient still suffered many complications after the severe metabolic insult with hypoxic ischemic encephalopathy, cerebral atrophy, global developmental delay and cortical visual impairment.
  
  
  CONCLUSIONS
  Because of the lack of expanded newborn screening in Hong Kong, this child unfortunately presented in the most severe form of tyrosinemia type I. Expanded newborn screening can save life and reduce the burden of diagnostic complexity. This illustrates the need for expanded newborn screening in Hong Kong.
authors.affiliation: Kowloon West Cluster Laboratory Genetic Service, Department of Pathology, Princess Margaret Hospital, Hong Kong, China. makm@ha.org.hk
authors.forename: Chloe Miu
authors.initials: CM
authors.lastname: Mak
authors.forename: Ching-Wan
authors.initials: CW
authors.lastname: Lam
authors.forename: Stella
authors.initials: S
authors.lastname: Chim
authors.forename: Tak-Shing
authors.initials: TS
authors.lastname: Siu
authors.forename: King-Fai
authors.initials: KF
authors.lastname: Ng
authors.forename: Sidney
authors.initials: S
authors.lastname: Tam
mesh_terms: D006723:Hong Kong; D006801:Humans; D006867:Hydrolases / Q000235:genetics*; D007223:Infant; D007231:Infant, Newborn; D017093:Liver Failure / Q000209:etiology / Q000235:genetics; D008297:Male; D009154:Mutation; D015997:Neonatal Screening; D020176:Tyrosinemias / Q000175:diagnosis* / Q000209:etiology / Q000235:genetics*
chemical_list: D006867:Hydrolases; C020156:fumarylacetoacetase