tyrosinemia type I

Tyrosinemia type I is an inherited metabolic disorder characterized by impaired breakdown of the amino acid tyrosine due to deficient activity of the enzyme fumarylacetoacetate hydrolase (FAH). This deficiency leads to progressive liver disease, renal tubular dysfunction, and metabolic disturbances. The condition is caused by pathogenic variants in the FAH gene and is inherited in an autosomal recessive pattern, meaning that affected individuals have received an altered gene copy from each parent. Prevalence estimates are not well established, underscoring its rarity, and early identification is important for implementing appropriate management strategies.

The clinical presentation of tyrosinemia type I is multi-system and variable. Hepatic involvement is a central feature, with nearly all individuals experiencing hepatic failure, hepatomegaly, and ascites. Renal manifestations include enlarged kidneys and impaired tubular function, while metabolic abnormalities such as hypoglycemia and metabolic acidosis are also common. Gastrointestinal symptoms, including episodic vomiting, melena, and anemia, may occur, and many patients also exhibit growth delay and fever. Not all individuals experience all features, and severity varies considerably.

Tyrosinemia type I results from disease-causing variants in the FAH gene, which lead to a deficiency of the enzyme fumarylacetoacetate hydrolase. The lack of functional FAH disrupts the normal metabolic breakdown of tyrosine, allowing toxic intermediates to accumulate and damage the liver and kidneys. This condition is inherited in an autosomal recessive pattern, which means that both parents must carry and pass on an altered copy of the FAH gene for a child to be affected. Families are encouraged to seek genetic counseling for further information and support regarding family planning.

Currently, management focuses on supportive care and symptom alleviation, with treatment tailored to the individual’s needs. A multidisciplinary care approach is critical; patients benefit from regular surveillance through scheduled evaluations that monitor liver function, kidney health, and metabolic stability. Long-term surveillance and collaborative care from specialists such as hepatologists, nephrologists, and metabolic experts help to detect complications early and guide treatment decisions. Genetic counseling is also recommended to assist families in understanding the condition and evaluating family planning options.

The outlook for individuals with tyrosinemia type I is highly variable and depends on the degree of liver and kidney involvement as well as the timeliness of diagnosis and access to specialized care. With current standards of care, many individuals experience improvements in quality of life and can reach adulthood, although the course of the condition may progress, stabilize, or vary between patients. Outcomes described in medical literature continue to evolve as standards of care improve. Families are advised to connect with metabolic and liver specialists and to consider genetic counseling for ongoing support and guidance.

Clinical trials are underway exploring new treatment approaches for tyrosinemia type I. Individuals interested in clinical trials can search ClinicalTrials.gov or consult their care team about eligibility.