title: Tyrosinemia type 1: a rare and forgotten cause of reversible hypertrophic cardiomyopathy in infancy.
abstract: BACKGROUND
  Tyrosinemia type 1 (TT1) is an autosomal recessive disorder caused by deficiency of the enzyme fumarylacetoacetate hydrolase (FAH). TT1 usually presents in infancy with features suggestive of liver disease or with sepsis-like symptoms.
  
  
  METHODS
  We report two Saudi siblings with TT1. Case 1 was a male infant who presented at 2 months old with fever, vomiting and refusal of feeding. Examination revealed a sick-looking infant with signs of severe dehydration and hypovolemic shock. He was jaundiced, and had hepatomegaly and elevated liver enzymes. Echocardiography was performed in light of a lack of response to inotropes, and revealed biventricular and interventricular septal hypertrophies. The ventricular ejection fraction was 65%. Urine organic acid analysis showed elevated succinylacetone, consistent with a diagnosis of TT1. An FAH gene study identified a c.1 A > G homozygous mutation. This patient responded well to intensive cardiorespiratory therapy, tyrosine-free formula, and oral 2-nitro-4- trifluoromethylbenzyl 1, 3 cyclohexanedione (NTBC). Echocardiographic findings reverted to normal after 4 weeks. Case 2 was the younger brother of Case 1, and was born 6 months after his brother had been confirmed with tyrosinemia. Pregnancy and delivery were uneventful. Serum amino acid and organic acid analyses 4 days after birth confirmed tyrosinemia. DNA analysis identified a c.1 A > G homozygous mutation, as in his brother. Echocardiography was normal. Special formula and NTBC were commenced on day 7 of life. The infant remained asymptomatic after 9 months of follow-up.
  
  
  CONCLUSIONS
  These cases highlight TT1 as a treatable cause of cardiomyopathy in children. It also supports the idea that early diagnosis and treatment may prevent the development of cardiomyopathy associated with tyrosinemia.
authors.affiliation: Department of Pediatrics, College of Medicine, King Saud University, Riyadh 31461, P,O, Box 2925, Saudi Arabia. sararmohamed@hotmail.com.
authors.forename: Sarar
authors.initials: S
authors.lastname: Mohamed
authors.forename: Mohammed A
authors.initials: MA
authors.lastname: Kambal
authors.forename: Nasir A
authors.initials: NA
authors.lastname: Al Jurayyan
authors.forename: Abdulrahman
authors.initials: A
authors.lastname: Al-Nemri
authors.forename: Amir
authors.initials: A
authors.lastname: Babiker
authors.forename: Rana
authors.initials: R
authors.lastname: Hasanato
authors.forename: Abdullah S
authors.initials: AS
authors.lastname: Al-Jarallah
mesh_terms: D002312:Cardiomyopathy, Hypertrophic / Q000150:complications / Q000235:genetics* / Q000473:pathology / Q000628:therapy; D003512:Cyclohexanones / Q000627:therapeutic use; D005526:Food, Formulated; D006537:Heptanoates / Q000652:urine; D006720:Homozygote; D006801:Humans; D006867:Hydrolases / Q000172:deficiency / Q000235:genetics*; D007223:Infant; D008297:Male; D009154:Mutation; D009579:Nitrobenzoates / Q000627:therapeutic use; D035781:Siblings; D016896:Treatment Outcome; D020176:Tyrosinemias / Q000150:complications / Q000235:genetics* / Q000473:pathology / Q000628:therapy
chemical_list: D003512:Cyclohexanones; D006537:Heptanoates; D009579:Nitrobenzoates; C020804:succinylacetone; D006867:Hydrolases; C020156:fumarylacetoacetase; C077073:nitisinone
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