Tyrosinemia or tyrosinaemia is an error of

metabolism Metabolism (, from el, μεταβολή ''metabolē'', "change") is the set of life-sustaining chemical reactions in organisms. The three main functions of metabolism are: the conversion of the energy in food to energy available to run ...

, usually inborn, in which the body cannot effectively break down the amino acid

tyrosine -Tyrosine or tyrosine (symbol Tyr or Y) or 4-hydroxyphenylalanine is one of the 20 standard amino acids that are used by cells to synthesize proteins. It is a non-essential amino acid with a polar side group. The word "tyrosine" is from the G ...

. Symptoms of untreated tyrosinemia include

liver The liver is a major organ only found in vertebrates which performs many essential biological functions such as detoxification of the organism, and the synthesis of proteins and biochemicals necessary for digestion and growth. In humans, it ...

and

kidney The kidneys are two reddish-brown bean-shaped organs found in vertebrates. They are located on the left and right in the retroperitoneal space, and in adult humans are about in length. They receive blood from the paired renal arteries; blo ...

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.

Cause

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

hepatocyte A hepatocyte is a cell of the main parenchymal tissue of the liver. Hepatocytes make up 80% of the liver's mass. These cells are involved in: * Protein synthesis * Protein storage * Transformation of carbohydrates * Synthesis of cholesterol, b ...

s, resulting in damage to the kidney and liver, respectively. Type II tyrosinemia results from a mutation in the ''TAT'' gene, which encodes the enzyme tyrosine aminotransferase. As a result of ''TAT'' deficiency, the substrate tyrosine accumulates, causing ophthalmologic and dermatologic abnormalities. Type III tyrosinemia results from a mutation in the ''HPD'' gene, which encodes the enzyme 4-hydroxyphenylpyruvate dioxygenase. Type III tyrosinemia is the rarest of the three conditions, with only a few cases ever reported. Most of those cases have included intellectual disability and neurologic dysfunction.

Diagnosis

Types

Type I tyrosinemia can be detected via blood tests for the presence of a fumarylacetoacetate metabolite, succinylacetone, which is considered a

pathognomonic Pathognomonic (rare synonym ''pathognomic'') is a term, often used in medicine, that means "characteristic for a particular disease". A pathognomonic sign is a particular sign whose presence means that a particular disease is present beyond any doub ...

indicator for the disease. 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. Inborn errors of metabolism of phenylalanine and tyrosine

Inborn errors of metabolism of phenylalanine and tyrosine

Treatment

Treatment varies depending on the specific type; a low-protein diet combined with the use of a specially engineered formula to supply protein is required in most cases. Experience with nitisinone has shown it to be effective, especially when started within the first month of life, and it is now the standard course of treatment. It is a 4-hydroxyphenylpyruvate dioxygenase inhibitor indicated for the treatment of

hereditary Heredity, also called inheritance or biological inheritance, is the passing on of traits from parents to their offspring; either through asexual reproduction or sexual reproduction, the offspring cells or organisms acquire the genetic info ...

tyrosinemia type 1 (HT-1) in combination with dietary restriction of tyrosine and

phenylalanine Phenylalanine (symbol Phe or F) is an essential α-amino acid with the formula . It can be viewed as a benzyl group substituted for the methyl group of alanine, or a phenyl group in place of a terminal hydrogen of alanine. This essential amino a ...

Liver transplant Liver transplantation or hepatic transplantation is the replacement of a diseased liver with the healthy liver from another person (allograft). Liver transplantation is a treatment option for end-stage liver disease and acute liver failure, a ...

is indicated for patients with tyrosinemia type I who do not respond to nitisinone, as well as those with acute liver failure and hepatomas.

References

External links