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This can lead to a fatty liver and the development of tumors in areas affected by this scarring of liver tissue. These scars are known as nodules. There is a 37% chance of developing a hepatocellular carcinoma (HCC) for untreated patients. Renal and neurological manifestations
Many patients display impaired kidney function and neurological symptoms. In addition to liver cells, kidney cell expression involves expression of the gene for FAH. Kidney failure is a potential result of impaired kidney function, but the most common symptom associated with renal dysfunction is hypophosphatemic rickets. Neurological manifestations are characterized by acute neurological crises due to overaccumulation of porphyrin. These crises are characterized by porphyria. They typically follow an infection. Patients can present with a variety of varied symptoms including paresthesias, abdominal pain, pain-induced seizures, and can result in self-mutilation in response to this pain. Episodes can last for 1–7 days and can lead to neuropathy. Genetics
Tyrosinemia type I is an autosomal recessive inherited condition. Mutant alleles in the gene are inherited from both parents. The genetic mutation occurs to the fumarylacetoacetate hydrolase (FAH) enzyme gene, located on chromosome 15. The most common mutation is IVS12+5(G->A) which is a mutation in the splice site consensus sequence of intron 12, therefore affecting exon 12. A second allele is the IVS6-1(G-T) mutation. This mutation results in a nonfunctional enzyme.Type 1 tyrosinemia is inherited in an autosomal recessive pattern. Pathophysiology
Fumarylacetoacetate hydrolase catalyzes the final step in the degradation of tyrosine - fumarylacetoacetate to fumarate, acetoacetate and succinate.