Tyrosinemia or tyrosinaemia is an error of metabolism, usually inborn, in which the body cannot effectively break down the amino acid tyrosine. Symptoms of untreated tyrosinemia include liver and kidney disturbances. Without treatment, tyrosinemia leads to liver failure. Today, tyrosinemia is increasingly detected on newborn screening tests before any symptoms appear. With early and lifelong management involving a low-protein diet, special protein formula, and sometimes medication, people with tyrosinemia develop normally, are healthy, and live normal lives.

Signs and symptoms

Cause

thumb|left|140 px|Tyrosinemia is inherited in an [[autosomal recessive pattern.]]

All tyrosinemias result from dysfunction of various genes in the phenylalanine and tyrosine catabolic pathway, and are inherited in an autosomal-recessive pattern.

Type I tyrosinemia results from a mutation in the FAH gene, which encodes the enzyme fumarylacetoacetase. As a result of FAH deficiency, the substrate fumarylacetoacetate can accumulate in proximal renal tubular cells and hepatocytes, resulting in damage to the kidney and liver, respectively. Most of those cases have included intellectual disability and neurologic dysfunction.

Type II tyrosinemia can be detected via the presence of significantly elevated plasma tyrosine levels, and the diagnosis can be confirmed by detection of a mutation in TAT in cultured fibroblasts.

Type III tyrosinemia can be diagnosed by detection of a mutation in HPD in cultured fibroblasts. Liver transplant is indicated for patients with tyrosinemia type I who do not respond to nitisinone, as well as those with acute liver failure and hepatomas.

See also

  • Alkaptonuria
  • Inborn error of metabolism
  • Ochronosis

References

  • GeneReview/NCBI/NIH/UW entry on Tyrosinemia Type 1
  • Tyrosinemia on Genetic Home Reference