Modern ideas about the most severe variant of hereditary tyrosinemia are reflected -- its first type related to orphan diseases (the population frequency of occurrence is 1: 100,000-120,000 live newborns). The latest data on etiology is highlighted (mutations in the gene for the enzyme fumarylacetoacetase (FAA), leading to a deficiency of fumarylacetohydrolase (FAH), the last enzyme in tyrosine catabоlism; the genetic mutation is localized on human chromosome 15q23-q25 and consists of 14 exons) and the mechanisms of development of the disease ( the bypass abnormal pathway of tyrosine metabolism with the formation of highly toxic and carcinogenic metabolites -- succinyl acetoacetate (SAA) and succinylacetone (SA), others; substrate accumulation mainly in FAH-deficient hepatocytes and proximal renal tubule cells; violation of the processes of gluconeogenesis, ammonia detoxification and hepatic protein synthesis), which determine different clinical variants and symptom polymorphism. A modern classification of type I tyrosinemia and a detailed protocol for diagnostic examination of the patient, including instrumental methods, laboratory monitoring of highly toxic derivatives of the tyrosine metabolic pathway and molecular genetic studies, are presented. Denotes a range of diseases that should be carried out a differential diagnosis of tyrosinemia. The modern concept of treatment of this orphan disease (protein-free diet, specialized amino acid mixtures, hepatoprotectors, vitamin D and others) is laid out with an emphasis on enzyme replacement therapy with nitisinone, an enzyme inhibitor (4-hydroxyphenylpyruvate dioxygenase) of the first phase of tyrosine degradation. A description of a clinical case and a 15-year-old teenager with a hereditary tyrosinemia type I who received a low protein diet, the amino acid mixture «XPHEN TYR Tyrosidone» (Nutricia) and nitisinone (Orfadin®).