Tyrosinemia is caused when the body cannot effectively break down the tyrosine. If untreated, tyrosine and its byproducts build up in tissues and organs, leading to serious liver and kidney disturbances.
Mutation in the Fumarylacetoacetate-hydroxylase (FAH) gene, Aminotransferase (TAT) gene and Hydroxyphenylpyruvate-dioxygenase (HPD) gene are all responsible for tyrosine degradation pathway.
- Type I tyrosinemia: can be caused by mutationsin the FAH gene.
- Type II tyrosinemia: can be confirmed by detection of a mutation in TAT gene in cultured fibroblasts.
- Type III tyrosinemia: mutation in the HPDgene in cultured fibroblasts.
- Intellectual disability
- Periodic loss of balance and coordination (intermittent ataxia)
- Increased tendon reflexes
Metabolic Pathway for Phenylalanine and Tyrosine
Dysfunction of various genes in the phenylalanine and tyrosine catabolic pathway results in all the types of tyrosinemias and are inherited in an autosomal-recessive pattern.