Tyrosinemia

Tyrosinemia is a genetic disorder characterized by the body's inability to effectively break down the amino acid tyrosine, leading to a toxic buildup in organs and tissues.

Overview

Tyrosinemia occurs when the body cannot properly break down tyrosine, a building block of most proteins. If untreated, the accumulation of tyrosine and its byproducts can cause serious health complications. There are three distinct types of the disorder, each with different genetic causes and symptoms.

Types of Tyrosinemia

Tyrosinemia Type I

The most severe form, usually beginning in the first few months of life. Symptoms include failure to thrive, jaundice, a cabbage-like odor, and an increased tendency to bleed. It can lead to liver and kidney failure, softening of the bones (rickets), and an increased risk of hepatocellular carcinoma. Some children experience neurologic crises involving abdominal pain and respiratory failure.

Tyrosinemia Type II

Typically begins in early childhood and affects the eyes, skin, and mental development. Symptoms include eye pain, redness, sensitivity to light (photophobia), and thick, painful skin on the palms and soles (palmoplantar hyperkeratosis). About half of those affected have some degree of intellectual disability.

Tyrosinemia Type III

The rarest form. Characteristic features include intellectual disabilities, seizures, and periodic loss of balance and coordination (intermittent ataxia).

Causes

Tyrosinemia is caused by variants in the FAH, TAT, or HPD genes. These genes provide instructions for enzymes involved in the five-step process of breaking down tyrosine. When these enzymes are deficient, toxic byproducts accumulate, damaging the liver, kidneys, and nervous system.

Inheritance

All forms of tyrosinemia are inherited in an autosomal recessive pattern, meaning both copies of the gene in each cell must have a variant to cause the disorder.