First Macedonian child with tyrosinemia type 1 successfully treated with nitisinone and report of a novel mutation in the FAH gene

Abstract

Introduction. Hereditary tyrosinemia type 1 (HT1) is a severe hereditary metabolic disorder of tyrosine metabolism due to fumarylacetoacetate hydrolase (FAH) deficiency and accumulation of toxic products in tissues. More than 80 mutations in the FAH gene are presently reported on the Human Genome Mutation Database. To date, no molecular genetic defects of HT1 in Macedonia have been described. Case outline. A female infant two and a half months old presented with failure to thrive, anemia, edemas, and severe coagulation disturbances. The diagnosis of HT1 was based on high levels of serum ?-fetoprotein, increased serum tyrosine, and positive succinylacetone in urine. Nitisinone treatment with tyrosine-restriction diet was immediately introduced. The patient, currently aged five years, has normal growth, psychomotor development, and no focal lesions on abdominal MRI. A screening of the FAH gene revealed two heterozygous mutations ? c.[1A>G];[784T>A]. The mutation c.784T>A is a novel one (p.Trp262Arg), and was predicted to be the cause of the disease by an in silico analysis. Conclusion. To date, this case is the first and only child with HT1 successfully treated with nitisinone in our country. Also, this is the first report of an HT1 patient caused by the c.784T>A mutation.