[Clinical, biochemical and molecular characteristics in 11 Czech children with tyrosinemia type I].

摘要: Background Hereditary tyrosinemia type 1 (HT1) is a rare autosomal recessive inborn error of metabolism caused by deficiency fumarylacetoacetate hydrolase. HT1 manifests with severe liver and kidney impairment associates an increased risk cancer development. The aim our study to present detailed clinical picture results biochemical molecular genetic analyses in 11 Czech patients diagnosed clinic within 1982-2006. Methods In 9 the disease manifested between 1.5-7 months age refusal eat, failure thrive vomiting. 4 children progressed acute failure. One clinically healthy boy was because affected sister. one cirrhosis diagnosis delayed until 5.5 years. all investigation showed elevated enzymes, alpha1-fetoprotein hypophosphatemic rickets. Metabolic revealed plasma tyrosine level, urinary excretion succinylacetone 8 measured also delta-aminolevulinic acid concentration. Three born before 1988 died due development (two them) or average living 10.7 +/- 8.3 Mutation analysis FAH gene confirmed these three novel mutations were found gene: c.579C>A, c.680G>T c.1210G>A. Clinical status six favourable on strict low protein diet combined Orfadin therapy. However, two despite maximal available therapy lasting 2 10 years resp., towards necessity transplantation. Conclusions Early diagnostics as part extended newborn screening only possibility further improve prognosis patients. Moreover, molecular-genetic enables prenatal families.