SCIENTIFIC BACKGROUND

FAH

Tyrosinemia type I is an autosomal recessive inherited metabolic disorder belonging to the group of amino acid metabolism defects. The prevalence is about 1:100,000. The disease is based on a deficiency of the enzyme fumarylacetoacetate hydrolase, which blocks tyrosine metabolism at the final step. This leads to accumulation of the metabolites maleyl acetoacetate and fumaryl acetoacetate, which are converted into succinyl acetoacetate and succinyl acetone. These substances have toxic effects on the liver and kidney and also inhibit the enzyme delta-aminolevulinate dehydratase, a key enzyme in porphobilinogen synthesis.

 

The clinical picture is highly variable. Different forms of tyrosinemia type I are distinguished according to the age of initial presentation. The acute form presents primarily with severe liver disease in the first weeks and months of life. The chronic form manifests clinically later and is associated with a variety of symptoms, particularly liver and kidney dysfunction and vitamin D-independent rickets. All forms are at high risk for hepatocellular carcinoma. In addition, porphyria-like symptoms also occur. Treatment with nitisinone and a low-tyrosine diet alleviates the symptoms and progression of the disease.

 

The fumarylacetoacetate hydrolase deficiency is caused by pathogenic variants in the FAH gene. The splice variants c.554-1G>T (IVS6-1G>T) and c.1062+5G>A (IVS12+5G>A) are frequently causative for the disease in the northwestern European population and in the Mediterranean region.

 

Diagnosis of tyrosinemia type 1 is part of newborn screening, and if the findings are abnormal, the diagnosis can be confirmed by molecular genetics. The disease is treatable with nitisinone and a low protein diet.

 

References
Prescribing information Orfadin® / Sniderman King et al. 2014, Tyrosinaemia Type I, Gene Reviews / de Lae et al. 2013, Orphanet Journal of Rare Diseases 8:8 / Bergmann et al. 1998, Hum Mutat. 12:19

GENES

FAH

ASSOCIATED TESTS

How to order

LATEST ARTICLES

Every year on April 25th, DNA Day celebrates the discovery of DNA’s double helix and the advances we’ve made in understanding genetics. D...

Read more

Neurodevelopmental disorders (NDDs) have diverse genetic origins, making diagnosis challenging. A new study analyzing over 1,100 pediatric patients f...

Read more

Colorectal cancer (CRC) remains one of the most prevalent and deadly cancers worldwide, with a significant number of cases presenting at an advanced ...

Read more

Carrier screening is a genetic test designed to identify whether an individual carries a gene with changes (mutations) associated with inherited diso...

Read more

Trisomy 13, also known as Patau syndrome, is a genetic condition in which cells in the body have three copies of chromosome 13 instead of two. The co...

Read more

The human brain develops through a complex series of events, with genes carefully regulating the formation of neurons and glial cells. A recent study...

Read more

Rare diseases affect between 300 and 400 million people worldwide – more than cancer and AIDS combined [1, 2], but despite this, many people face a...

Read more

Rosalind Elsie Franklin was a brilliant and meticulous research scientist whose interdisciplinary work made fundamental contributions to various area...

Read more

February, designated as Cancer Awareness Month, marks a time to reflect on the remarkable progress made in cancer research and to inspire hope for th...

Read more

Introduction Cardiovascular disease (CVD) is a major health issue as it remains a leading cause of death worldwide [1]. CVD is responsible for mor...

Read more