Hyperlysinemia is an inherited condition characterized by elevated blood levels of the amino acid lysine, a building block of most proteins. Hyperlysinemia is caused by the shortage (deficiency) of the enzyme that breaks down lysine. Hyperlysinemia typically causes no health problems, and most people with elevated lysine levels are unaware that they have this condition. Rarely, people with hyperlysinemia have intellectual disability or behavioral problems. It is not clear whether these problems are due to hyperlysinemia or another cause.

Mutations in the AASS gene cause hyperlysinemia. The AASS gene provides instructions for making an enzyme called aminoadipic semialdehyde synthase. This enzyme performs two functions in the breakdown of lysine. First, the enzyme breaks down lysine to a molecule called saccharopine. It then breaks down saccharopine to a molecule called alpha-aminoadipate semialdehyde.

Mutations in the AASS gene that impair the breakdown of lysine result in elevated levels of lysine in the blood and urine. These increased levels of lysine do not appear to have any negative effects on the body.

When mutations in the AASS gene impair the breakdown of saccharopine, this molecule builds up in blood and urine. This buildup is sometimes referred to as saccharopinuria, which is considered to be a variant of hyperlysinemia. It is unclear if saccharopinuria causes any symptoms.

Normal Function

The AASS gene provides instructions for making an enzyme called aminoadipic semialdehyde synthase. This enzyme is found in most tissues, with the highest amounts found in the liver. Aminoadipic semialdehyde synthase is involved in the breakdown of the amino acid lysine, a building block of most proteins. It is called a bifunctional enzyme because is performs two functions. One function, called lysine-ketoglutarate reductase, breaks down lysine to a molecule called saccharopine. The other function, called saccharopine dehydrogenase, breaks down saccharopine to a molecule called alpha-aminoadipate semialdehyde.

Health Conditions Related to Genetic Changes

Hyperlysinemia

At least five mutations in the AASS gene have been found to cause hyperlysinemia. Most of these mutations change single amino acids in aminoadipic semialdehyde synthase. These mutations are thought to decrease or eliminate enzyme activity, resulting in an inability to break down lysine. Lysine that is not broken down accumulates in the blood, but it typically causes no health problems.

When mutations in the AASS gene impair the breakdown of saccharopine, this molecule builds up in blood and urine. This buildup is sometimes referred to as saccharopinuria, which is considered to be a variant of hyperlysinemia. It is unclear if saccharopinuria causes any symptoms.

Other Names for This Gene

• AASS_HUMAN
• alpha-aminoadipate semialdehyde synthase
• aminoadipic semialdehyde synthase
• LKR/SDH
• LKRSDH
• lysine-2-oxoglutarate reductase
• lysine-ketoglutarate reductase /saccharopine dehydrogenase

Genomic Location

This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.

The incidence of hyperlysinemia is unknown.