glutamate formiminotransferase deficiency

Glutamate formiminotransferase deficiency, also known as glutamate formimidoyltransferase deficiency, is an inherited disorder that affects physical and mental development.

Types of Glutamate Formiminotransferase Deficiency

There are two forms of this condition, which are distinguished by the severity of symptoms. The mild form is characterized by minor delays in physical and mental development, while the severe form can lead to more significant developmental issues and intellectual disability [3][4].

Causes and Symptoms

Glutamate formiminotransferase deficiency is caused by mutations in the FCTD gene, which codes for the enzyme formiminotransferase cyclodeaminase (FTCD). This enzyme plays a crucial role in breaking down histidine, an amino acid that makes up proteins. The deficiency leads to elevated levels of formiminoglutamate in urine and plasma [9].

Symptoms associated with glutamate formiminotransferase deficiency include:

• Minor delays in physical and mental development (mild form)
• More significant developmental issues and intellectual disability (severe form)

Prevalence

Glutamate formiminotransferase deficiency is a rare disorder, with approximately 20 affected individuals identified [5].

Genetic Basis

The condition is inherited in an autosomal recessive manner, meaning that both parents must be carriers of the mutated gene for their child to inherit the condition. The FCTD gene is responsible for encoding the FTCD enzyme, which plays a critical role in folate metabolism and transport.

Overall, glutamate formiminotransferase deficiency is a rare genetic disorder that affects physical and mental development, with two distinct forms of severity.

Glutamate formiminotransferase deficiency, also known as FTCD, is a rare inherited disorder that affects physical and mental development. The signs and symptoms of this condition can vary widely, but they often include:

• Developmental delays: People with glutamate formiminotransferase deficiency may experience minor to significant delays in physical and mental development.
• Intellectual disabilities: Some individuals with FTCD may have mild intellectual disability, while others may have more severe cognitive impairments.
• Seizures: Seizures are a common symptom of glutamate formiminotransferase deficiency, and they can range from mild to severe in intensity.
• Neurological abnormalities: Other neurological symptoms associated with FTCD include muscle weakness, spasticity, and coordination problems.

According to MedlinePlus Genetics [12], the severity of symptoms can vary widely among individuals with glutamate formiminotransferase deficiency. Some people may experience only minor delays in physical and mental development, while others may have more severe cognitive and motor impairments.

It's worth noting that the symptoms of FTCD can be nonspecific and overlap with other genetic diseases [13]. Therefore, testing for glutamate formiminotransferase deficiency is necessary to confirm a diagnosis. Unfortunately, there are currently no treatments known to prevent or delay the signs and symptoms of this condition [14][15].

References: [12] MedlinePlus Genetics: Glutamate formiminotransferase deficiency [13] Clinical resource with information about Glutamate formiminotransferase deficiency and its clinical features, FTCD [14] Glutamate formiminotransferase deficiency is an inherited metabolic

Glutamate formiminotransferase deficiency can be diagnosed through various genetic tests that detect mutations in the FTCD gene.

• Next-generation sequencing (NGS) test: This test is suitable for individuals with clinical signs and symptoms, suspicion of, or family history of glutamate formiminotransferase deficiency. It detects sequence variants and/or copy number variants within the FTCD gene with >99% sensitivity [4].
• Deletion/duplication analysis: This type of testing can identify potential genetic causes for a condition and inform prognosis and clinical management [9, 10]. Deletion/duplication analysis is offered by Centogene AG - the Rare Disease Company [10] and Fulgent Genetics [11].
• Sanger sequencing: This method has been used to identify biallelic mutations in the FTCD gene in patients with glutamate formiminotransferase deficiency [6, 7].

These diagnostic tests can help confirm a diagnosis of glutamate formiminotransferase deficiency and provide valuable information for clinical management.

References:

[4] - This is a next generation sequencing (NGS) test appropriate for individuals with clinical signs and symptoms, suspicion of, or family history of Glutamate Formiminotransferase Deficiency. Sequence variants and/or copy number variants within the FTCD gene will be detected with >99% sensitivity. [6] - In 3 patients with glutamate formiminotransferase deficiency, including 2 sibs, Hilton et al. (2003) identified compound heterozygous mutations in the FTCD gene (606806.0001-606806.0003). [7] - Clinical features ; Abnormality of blood and blood-forming tissues. Megal

Treatment Overview

Glutamate formiminotransferase deficiency, also known as formiminoglutamic aciduria, is a rare genetic disorder that affects the body's ability to break down the amino acid histidine. While there are no known treatments that can prevent or delay its signs and symptoms, treatment is generally focused on managing the condition and alleviating its effects.

Current Treatment Options

• No specific treatment: As of 2021, there are no known treatments for glutamate formiminotransferase deficiency that will prevent or delay its signs and symptoms [9].
• Supportive care: Babies and children with glutamate formiminotransferase deficiency typically do not need any treatment. However, if your baby does have signs and symptoms of the condition, it is essential to talk to your healthcare provider about which treatment(s), if any, your baby needs [3].

Management Strategies

• Monitoring: Regular monitoring of the child's development and health status is crucial in managing glutamate formiminotransferase deficiency.
• Nutritional support: Ensuring adequate nutrition and hydration can help alleviate some symptoms associated with the condition.

Future Research Directions

While there are no known treatments for glutamate formiminotransferase deficiency, research into this area continues. Further studies may lead to the development of new treatment options or improved management strategies for individuals affected by this condition.

References:

[3] - Treatment and Management. [9] - As of 2021, there are no known treatments for this disorder that will prevent or delay its signs and symptoms. Medical Conditions Associated with Excess ... [9]

Differential Diagnosis of Glutamate Formiminotransferase Deficiency

Glutamate formiminotransferase deficiency is a rare genetic disorder that affects physical and mental development. When diagnosing this condition, it's essential to consider other possible causes of similar symptoms. Here are some differential diagnoses to consider:

• Hereditary folate malabsorption (HFM): This condition also involves impaired folate metabolism, leading to megaloblastic anemia, growth retardation, and mental sub-normality [10].
• Megaloblastic anemia: This type of anemia can be caused by a deficiency in vitamin B12 or folate, which are essential for DNA synthesis. It's characterized by large red blood cells that are not able to function properly [11].
• Histidine catabolism disorders: Glutamate formiminotransferase deficiency is involved in the breakdown of histidine, an amino acid. Other disorders affecting histidine metabolism could present with similar symptoms [9].
• Folate transport disorders: Conditions that affect folate transport into the central nervous system, such as hereditary folate malabsorption (HFM), can also lead to similar symptoms [11].

Key differences and distinguishing features

When differentiating glutamate formiminotransferase deficiency from other conditions, consider the following:

• Severity of symptoms: Glutamate formiminotransferase deficiency has two forms: a mild form with minor delays in physical and mental development, and a severe form with significant intellectual disability [2, 5, 12].
• Presence of anemia: While megaloblastic anemia is a feature of some differential diagnoses, it's not always present in glutamate formiminotransferase deficiency [10].
• Histidine levels: Elevated histidine levels may be indicative of disorders affecting histidine metabolism [9].

References

[2] - Context result 2 [5] - Context result 5 [9] - Context result 9 [10] - Context result 10 [11] - Context result 11 [12] - Context result 12