Conditions Guanidinoacetate Methyltransferase Deficiency

Guanidinoacetate methyltransferase (GAMT) deficiency is an inherited condition that affects the body’s ability to produce creatine. Without an adequate supply of creatine, the body is unable to use and store energy properly. This can cause severe neurological problems such as intellectual disability, limited speech development, recurrent seizures, behavioral problems, and involuntary movements. Fortunately, early diagnosis and treatment can lead to improved health and development in children affected by GAMT deficiency.

Condition Type

Other Disorders

Frequency

Guanidinoacetate methyltransferase (GAMT) deficiency is a very rare condition with less than 150 individuals diagnosed worldwide. In the United States, GAMT deficiency appears to be more common in Utah with one of every 120,000 babies affected by the condition.

Also known as

  • GAMT
  • GAMT
  • GAMT deficiency
  • Creatine deficiency syndrome due to GAMT deficiency

Follow-Up Testing

Your baby’s doctor may ask you if your baby is showing any of the signs of guanidinoacetate methyltransferase deficiency (see Early Signs, below). If your baby has certain signs, your baby’s doctor may suggest starting immediate treatment.

If your baby’s newborn screening result for guanidinoacetate methyltransferase (GAMT) deficiency was out of range, your baby’s doctor or the state screening program will contact you to arrange for your baby to have additional testing. It is important to remember that an out-of-range screening result does not necessarily mean that your child has the condition. However, it is very important that you go to your follow-up appointment for a confirmatory test. The harmful effects of untreated GAMT deficiency can occur in early infancy so follow-up testing must be conducted as soon as possible to determine whether or not your baby has the condition.

Follow-up testing will involve checking your baby’s blood and urine for signs of GAMT deficiency. Because GAMT deficiency affects the body’s ability to make creatine, babies with the condition often have reduced levels of creatine in their blood and urine. Affected babies may also have elevated blood and urine levels of guanidinoacetate, a compound that is typically used to make creatine. In babies with levels suggestive of GAMT deficiency, genetic testing is often recommended to confirm the diagnosis.

A specialized test called magnetic resonance (MR) spectroscopy may also be used to determine if creatine levels are reduced in the brain, specifically. MR spectroscopy is conducted on the same machine as conventional MRI with a series of additional tests (spectroscopy) added to measure biochemical changes in the brain.

About Guanidinoacetate Methyltransferase Deficiency

Early Signs

Children affected by guanidinoacetate methyltransferase (GAMT) deficiency can develop symptoms anytime from infancy (age 3-6 months) to age three years.

Early signs of GAMT deficiency may include:

  • Developmental delay
  • Poor muscle tone
  • Seizures
  • Involuntary movements
Treatment

Supplements

People affected by guanidinoacetate methyltransferase (GAMT) deficiency generally require lifelong treatment with creatine monohydrate and ornithine supplements.

Creatine is a substance that is naturally produced in the body. It allows the body to properly store and use energy. Because GAMT deficiency impairs the body’s ability to produce creatine, affected people often have reduced levels throughout their body. The goal of creatine monohydrate supplementation is to ensure that all parts of the body (especially those that require large amounts of energy, such as the brain) have an adequate supply of creatine to function properly.

Ornithine supplementation may be prescribed to reduce the high levels of guanidinoacetate that accumulate in the blood and tissues of people affected by GAMT deficiency. This treatment is important because elevated levels of guanidinoacetate can be toxic to the nervous system.

Dietary Treatment

With the guidance of a metabolic specialist, people with GAMT deficiency often follow a natural-protein restricted diet (dietary restriction of arginine). This special diet, in combination with ornithine supplementation, can help prevent the accumulation of guanidinoacetate in the nervous system. Medical foods and formulas may be recommended to ensure that affected children have the nutrients necessary for proper growth and development.

Expected Outcomes

Guanidinoacetate methyltransferase (GAMT) deficiency is a rare condition so there is limited information regarding the long-term outlook for affected people. However, studies suggest that children who are diagnosed early and receive treatment before they develop symptoms often remain healthy with normal development. This is why newborn screening for GAMT deficiency is so important.

Without treatment, people affected by GAMT deficiency may develop:

  • Mild to severe intellectual disability
  • Significant developmental delay
  • Recurrent seizures that may be resistant to medications
  • Movement disorders
  • Behavioral problems (such as autism spectrum disorder, self-injurious behaviors, hyperactivity, aggressive behavior)
Causes

Guanidinoacetate methyltransferase (GAMT) deficiency is caused by changes (mutations) in the GAMT gene. This gene provides instructions for making an enzyme that helps the body produce creatine from a compound called guanidinoacetate. Mutations in the GAMT gene result in decreased levels of functional enzyme which impairs the body’s ability to create creatine. Because creatine is needed for the body to store and use energy, reduced levels may prevent certain organs and tissues from working properly. The effects of GAMT deficiency are most severe in organs and tissues that require large amounts of energy, such as the brain and muscles.

Without functional enzyme to convert guanidinoacetate to creatine, guanidinoacetate may accumulate in the blood and tissues of people affected by GAMT deficiency. Elevated levels of guanidinoacetate can be toxic to the central nervous system and contribute to the signs and symptoms associated with the condition.

GAMT deficiency is an autosomal recessive genetic condition. This means that a child must inherit two copies of the non-working gene, one from each parent, in order to have the condition. The parents of a child with an autosomal recessive condition each carry one copy of the non-working gene, but they typically do not show signs and symptoms of the condition.

While having a child with GAMT deficiency is rare, when both parents are carriers, they can have more than one child with the condition. Learn more about autosomal recessive inheritance.

Support for Guanidinoacetate Methyltransferase Deficiency

Support Services

Support groups can help connect families who have a child or other family member affected with guanidinoacetate methyltransferase deficiency with a supportive community of people who have experience and expertise in living with the condition. These organizations offer resources for families, affected individuals, health care providers, and advocates.

Accessing Care

Work with your baby’s doctor to determine the next steps for your baby’s care. Your baby’s physician may help you coordinate care with a doctor who specializes in metabolism or with other medical resources in your community.

Because guanidinoacetate methyltransferase (GAMT) deficiency is a genetic condition, you may want to talk with a genetics specialist. A genetic counselor or geneticist can help you understand the causes of the condition, discuss genetic testing for GAMT deficiency, and understand what this diagnosis means for other family members and future pregnancies. Speak with your baby’s doctor about getting a referral. The Clinic Services Search Engine offered by the National Coordinating Center for the Regional Genetic and Newborn Screening Service Collaboratives and the Find a Genetic Counselor tool on the National Society of Genetic Counselors (NSGC) website are two resources that can be used to identify local specialists.

Families' Experiences

One family shares their experience of raising two children with guanidinoacetate methyltransferase deficiency on the Children’s Hospital of Chicago’s website

Visit the Intermountain Primary Children’s Hospital website to see one family’s experience with guanidinoacetate methyltransferase deficiency and why they believe newborn screening for the condition is so important.

References & Sources

GeneReviews offers detailed information regarding the diagnosis, clinical characteristics, and treatment of guanidinoacetate methyltransferase deficiency.

Genetics Home Reference offers an information page on guanidinoacetate methyltransferase deficiency. Genetics Home Reference provides consumer-friendly information about the effects of genetic variation on human health.

The Genetic and Rare Diseases Information Center (GARD) offers information and resources regarding guanidinoacetate methyltransferase deficiency. GARD is a program of the National Center for Advancing Translational Sciences (NCATS) to provide access to current, reliable, and easy to understand information about rare or genetic diseases in English or Spanish.

ACT Sheets

Healthcare professionals can learn more about confirmatory testing by reading the American College of Medical Genetics and Genomics' Algorithm for Diagnosis and ACT Sheet, a guide for follow-up after newborn screening. You can visit this page of the ACMG website here.

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Last Reviewed - 08/07/2018