Glutamate formiminotransferase deficiency

Glutamate formiminotransferase deficiency is a rare inherited disorder affecting development, with symptoms ranging from mild developmental delays to severe intellectual disabilities and megaloblastic anemia.

Overview

Glutamate formiminotransferase deficiency is a rare inherited disorder that can affect development.

In the past, researchers recognized a mild form and a severe form of glutamate formiminotransferase deficiency. Researchers have since found people who received a diagnosis of glutamate formiminotransferase deficiency as infants who do not appear to have any related health problems. Researchers are actively working to learn more about this condition.

Symptoms

The signs and symptoms associated with glutamate formiminotransferase deficiency have ranged from mild developmental delays with high urine levels of a molecule called formiminoglutamate (FIGLU) to more severe intellectual disabilities and megaloblastic anemia. Megaloblastic anemia occurs when a person has a low number of red blood cells (anemia) and the remaining red blood cells are larger than normal (megaloblastic).

Frequency

Glutamate formiminotransferase deficiency has an estimated incidence of between 1 in 46,000 people and 1 in 60,000 people, but fewer than 100 people with this condition have been reported in the medical literature. Individuals with the severe form of the disorder have all been of Japanese ancestry.

Causes

Variants (also called mutations) in the FTCD gene cause glutamate formiminotransferase deficiency. The FTCD gene provides instructions for making an enzyme that is involved in the breakdown of histidine, which is a building block (amino acid) of many different proteins. One of the enzyme's jobs is to convert FIGLU to a molecule called 5-formiminotetrahydrofolate.

The FTCD gene variants that cause glutamate formiminotransferase deficiency alter the function of the FTCD enzyme, which disrupts the enzyme’s ability to completely break down histidine. This can cause FIGLU to build up in the body and be released in the urine. It is unclear exactly how these changes are related to the specific health problems seen in some people with glutamate formiminotransferase deficiency.

Inheritance

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

Other Names for This Condition

• Arakawa syndrome 1
• FIGLU-uria
• Formiminoglutamic acidemia
• Formiminoglutamic aciduria
• Formiminotransferase cyclodeaminase deficiency
• Formiminotransferase deficiency
• FTCD deficiency