Glutamate formiminotransferase deficiency is a rare inherited metabolic disorder that impacts the body’s ability to process a specific nutrient. This condition is classified as an autosomal recessive disorder, meaning an individual must inherit two altered copies of a gene, one from each parent, to develop it. It represents the second most common inborn error related to folate metabolism, and its presentation can vary significantly among affected individuals.
How the Body Uses Folate
Folate, also known as Vitamin B9, plays a wide range of roles in the body’s metabolic processes. It functions as a coenzyme in reactions that involve the transfer of single-carbon units, necessary for synthesizing nucleotides, the building blocks of DNA and RNA. Folate also participates in the metabolism of various amino acids, including methionine, serine, glycine, and histidine. This multifaceted involvement underscores its importance for proper cell function and overall health.
The formiminotransferase enzyme, encoded by the FTCD gene, is involved in a specific step within folate metabolism. This enzyme converts formiminoglutamate (FIGLU) to 5-formiminotetrahydrofolate. In individuals with glutamate formiminotransferase deficiency, the enzyme’s function is altered or reduced. This impaired function leads to an accumulation of FIGLU, which is then excreted in the urine. The accumulation of this compound can disrupt normal metabolic processes.
Recognizing the Signs
The signs associated with glutamate formiminotransferase deficiency can show a wide range of severity, from very mild to more pronounced. Some individuals diagnosed as infants have shown no related health problems. Those with a mild presentation may experience minor delays in physical and mental development, and a mild intellectual disability.
In contrast, the severe form of this disorder can present with profound intellectual disability. Affected individuals may also experience significant delays in developing motor skills, such as learning to sit, stand, or walk. The severe form is additionally characterized by megaloblastic anemia, where there is a reduced number of red blood cells, and the remaining cells are larger than normal. This type of anemia can lead to symptoms such as decreased appetite, a lack of energy, headaches, pale skin, and tingling or numbness in the hands and feet. Seizures and speech impairment have also been reported in some cases.
Diagnosis and Confirmation
Diagnosing glutamate formiminotransferase deficiency begins with a clinical evaluation based on observed symptoms and family history. Newborn screening programs may detect elevated levels of formiminoglutamate (FIGLU) in a baby’s blood spot, suggesting the possibility of the condition. However, an out-of-range screening result does not definitively confirm the diagnosis; further testing is necessary.
Specific laboratory tests are then used to confirm the condition. One such test measures the level of FIGLU in urine, which is elevated in affected individuals. Genetic testing is performed to identify variants in the FTCD gene, confirming the diagnosis. This involves analyzing DNA to pinpoint the specific genetic changes responsible for the enzyme’s impaired function.
Managing the Condition
Management approaches for glutamate formiminotransferase deficiency focus on supportive care to address individual symptoms. For many babies and children, especially those with mild or no apparent symptoms, specific medical treatment may not be required. If symptoms are present, interventions are tailored to the individual’s needs.
Folic acid supplementation may be recommended in some cases to help manage the condition. Dietary management, which may include limiting histidine intake, can also be considered. For neurological and developmental issues, various therapies play a role, including physical therapy for motor skill development, occupational therapy for daily living activities, and speech therapy for communication difficulties. The goal of management is to support the individual’s overall health and development.