What are the other Names for this Condition? (Also known as/Synonyms)

• AGAT Deficiency Disorder
• Arginine:Glycine Amidinotransferase Deficiency Disorder
• Creatine Deficiency Syndrome due to AGAT Deficiency
• GATM Deficiency Disorder

What is L-Arginine:Glycine Amidinotransferase Deficiency Disorder? (Definition/Background Information)

• L-Arginine:Glycine Amidinotransferase Deficiency Disorder (or AGAT Deficiency Disorder) is a rare condition that primarily affects the brain. People with AGAT Deficiency Disorder generally have mild to moderate intellectual disability
• Other signs and symptoms may include seizures, delayed language development, muscle weakness, failure to thrive, autistic behaviors, and delayed motor milestones (i.e., walking, sitting)
• Arginine:Glycine Amidinotransferase Deficiency Disorder is caused by changes (mutations) in the GATM gene and is inherited in an autosomal recessive manner
• Treatment of Arginine:Glycine Amidinotransferase Deficiency Disorder is focused on increasing cerebral creatine levels and generally consists of supplementation with creatine monohydrate

(Source: L-Arginine:Glycine Amidinotransferase Deficiency Disorder; Genetic and Rare Diseases Information Center (GARD) of National Center for Advancing Translational Sciences (NCATS), USA.)

Who gets L-Arginine:Glycine Amidinotransferase Deficiency Disorder? (Age and Sex Distribution)

• L-Arginine:Glycine Amidinotransferase Deficiency Disorder is a rare congenital disorder, with fewer than 20 cases being reported in the medical literature
• The presentation of symptoms typically occurs in infancy
• Both males and females may be affected
• Worldwide, individuals of all racial and ethnic groups may be affected

What are the Risk Factors for L-Arginine:Glycine Amidinotransferase Deficiency Disorder? (Predisposing Factors)

• A positive family history may be an important risk factor, since L-Arginine:Glycine Amidinotransferase Deficiency Disorder can be inherited
• Children born of consanguineous parents may bear an increased risk of developing this condition

It is important to note that having a risk factor does not mean that one will get the condition. A risk factor increases one’s chances of getting a condition compared to an individual without the risk factors. Some risk factors are more important than others.

Also, not having a risk factor does not mean that an individual will not get the condition. It is always important to discuss the effect of risk factors with your healthcare provider.

What are the Causes of L-Arginine:Glycine Amidinotransferase Deficiency Disorder? (Etiology)

• L-Arginine:Glycine Amidinotransferase Deficiency Disorder is caused by mutations in the GATM gene 
• This gene codes for the enzyme L-arginine:glycine amidinotransferase, and participates in the formation of creatine from the amino acids glycine, arginine and methionine in a two-step process
• The condition is inherited in an autosomal recessive manner

Autosomal recessive inheritance: Autosomal recessive conditions are traits or disorders that occur when two copies of an abnormal gene have been inherited on a non-sex chromosome. If both parents have an autosomal recessive condition, there is a 100% likelihood of passing on the mutated genes to their children. If, however, only one mutant copy of the gene is inherited, the individual will be a carrier of the condition, but will not be present with any symptoms. Children born to two carriers, have a 25% chance of being homozygous dominant (unaffected), a 50% chance of being heterozygous (carrier), and a 25% chance of being homozygous recessive (affected).

What are the Signs and Symptoms of L-Arginine:Glycine Amidinotransferase Deficiency Disorder?

The signs and symptoms of L-Arginine:Glycine Amidinotransferase Deficiency Disorder may include:

• Gowers sign
• Abnormality of creatine metabolism
• Autism
• Delayed speech and language development
• Failure to thrive
• Global developmental delay
• Intellectual disability
• Organic aciduria

(Source: L-Arginine:Glycine Amidinotransferase Deficiency Disorder; Genetic and Rare Diseases Information Center (GARD) of National Center for Advancing Translational Sciences (NCATS), USA.)

How is L-Arginine:Glycine Amidinotransferase Deficiency Disorder Diagnosed?

L-Arginine:Glycine Amidinotransferase Deficiency Disorder is diagnosed on the basis of the following information:

• Complete physical examination
• Thorough medical history evaluation
• Assessment of signs and symptoms
• Laboratory tests
• Imaging studies
• Biopsy studies, if necessary
• Molecular genetic testing to check for or confirm causative gene mutation(s)

Many clinical conditions may have similar signs and symptoms. Your healthcare provider may perform additional tests to rule out other clinical conditions to arrive at a definitive diagnosis.

What are the possible Complications of L-Arginine:Glycine Amidinotransferase Deficiency Disorder?

The complications of L-Arginine:Glycine Amidinotransferase Deficiency Disorder may include:

• Progressive muscle weakness
• Psychomotor delay, which can occur if no treatment is undertaken

Complications may occur with or without treatment, and in some cases, due to treatment also.

How is L-Arginine:Glycine Amidinotransferase Deficiency Disorder Treated?

There is no cure for L-Arginine:Glycine Amidinotransferase Deficiency Disorder, since it is a genetic condition. The treatment is usually given to manage the signs and symptoms and any complication that develops. This may include administering creatine supplementation to the affected individuals.

How can L-Arginine:Glycine Amidinotransferase Deficiency Disorder be Prevented?

Currently, L-Arginine:Glycine Amidinotransferase Deficiency Disorder may not be preventable, since it is a genetic disorder.

• Genetic testing of the expecting parents (and related family members) and prenatal diagnosis (molecular testing of the fetus during pregnancy), if available, may help in understanding the risks better during pregnancy
• If there is a family history of the condition, then genetic counseling will help assess risks, before planning for a child
• Active research is currently being performed to explore the possibilities for treatment and prevention of inherited and acquired genetic disorders

Regular medical screening at periodic intervals with tests and physical examinations are recommended.

What is the Prognosis of L-Arginine:Glycine Amidinotransferase Deficiency Disorder? (Outcomes/Resolutions)

• The prognosis of L-Arginine:Glycine Amidinotransferase Deficiency Disorder is dependent upon the severity of the signs and symptoms and associated complications, if any
• Early creatine supplementation is reported to improve muscle strength significantly. However, verbal and cognitive shortcomings may show only moderate improvement
• Typically, the prognosis may be assessed on a case-by-case basis

Additional and Relevant Useful Information for L-Arginine:Glycine Amidinotransferase Deficiency Disorder:

• L-Arginine:Glycine Amidinotransferase Deficiency Disorder is also known as Arginine:Glycine Amidinotransferase Deficiency Disorder

The following DoveMed website link is a useful resource for additional information:

http://www.dovemed.com/diseases-conditions/rare-disorders/