Guanidinoacetate methyltransferase deficiency (GAMT deficiency) is a genetic, metabolic condition that affects how the body produces creatine.^1,2 Creatine is important for energy production especially in the muscles and brain.¹ In people with GAMT deficiency, the body cannot properly convert guanidinoacetate (GAA) to creatine. This leads to low levels of creatine, which affects the body’s energy production and can impair brain and muscle function. There is also a build-up of GAA, which can be toxic to the brain (neurotoxic).^3,4 This can result in developmental delay, speech delay, intellectual disability, seizures, as well as behavioural and movement issues.

In Australia, GAMT deficiency has usually been diagnosed after symptoms develop. GAMT deficiency is in the process of being added to Australia’s newborn bloodspot screening (NBS) programs. For more information, please visit the Australian Government Department of Health, Disability and Ageing: What is screened in the program page. Studies have shown that children with GAMT deficiency who are diagnosed early and treated before symptoms develop can remain healthy and have normal development.^4-7

Synonyms: Cerebral creatine deficiency syndrome type 2; deficiency of guanidinoacetate methyltransferase; disorder of guanidinoacetate n-methyltransferase activity; gamt deficiency; guanidinoacetate n-methyltransferase activity disease²

Universal rare disease classifications provide a common language for recording, reporting and monitoring diseases. Please visit the Rare Disease Classifications page for more information about these internationally recognised classifications.

ORPHA:382 Guanidinoacetate methyltransferase deficiency

ICD-11: 5C53.4 Disorders of creatine metabolism

Symptoms of GAMT deficiency often presents between 3 months to 3 years of age and can vary between individuals.^1,2,8

If a child with GAMT deficiency is diagnosed early and treated before symptoms appear, the child can grow and develop in a similar way to their healthy peers who don’t have GAMT deficiency.^4-6 However, if not diagnosed and treated early, the child may have:^1-3,8-10

• developmental delay
• impaired speech
• intellectual disability
• hypotonia (weak muscle tone) and movement disorders
• behavioural changes
• seizures

Please speak to your medical team to learn more about the symptoms and health implications of GAMT deficiency.

Rare diseases are often serious and progressive, exhibiting a high degree of symptom complexity, leading to significant disability. Majority of the estimated two million Australians living with a rare disease meet the Australian Government’s definition for disability (in accordance to the Australian Public Service Commission and Australian Bureau of Statistics), and many experience severe and permanent disability impacts. If you or someone you care for is experiencing disability-related impacts from a rare condition, please speak with a health or disability professional for advice. Information about relevant disability support can be found at the RARE Portal’s Disability Support Information page.

GAMT deficiency is a genetic condition. It is caused by disease-causing genetic changes (variants) in the GAMT gene located on Chromosome 19.¹¹

All individuals have two copies (alleles) of the GAMT gene – one on each chromosome that is inherited from each parent. GAMT deficiency is an autosomal recessive condition, which means both copies of the GAMT gene must have the disease-causing genetic variants. More information on autosomal recessive inheritance pattern can be found at Centre for Genetics Education: Autosomal recessive inheritance.

If you would like to learn more about the inheritance and impact of this condition, please ask your doctor for a referral to a genetic counsellor. Genetic counsellors are qualified allied health professionals who can provide information and support regarding genetic conditions and testing. More information about genetic counselling can be found at:

• Information on Genetic Services
• The National and State Services pages underneath the ‘Genetic Counselling’ sections listed

In Australia, GAMT deficiency is usually diagnosed after symptoms develop and may involve testing blood and urine samples to measure levels of creatine (Cr), guanidinoacetate (GAA) and creatinine (Crn). Elevated (higher than normal) levels of GAA, reduced levels of Cr and low to normal levels of Crn would be indicative of GAMT deficiency.^1,3

Diagnosis of GAMT deficiency is usually confirmed by genetic testing to identify disease-causing genetic variants in the GAMT gene and imaging of the brain using magnetic resonance spectroscopy (MRS) to measure creatine in the brain.^1,3

GAMT deficiency is in the process of being added to Australia’s newborn bloodspot screening (NBS) programs. For more information, please visit the Australian Government Department of Health, Disability and Ageing: What is screened in the program page.

Please speak to your medical team to learn more about the available pathways for diagnosis of this condition.

Treatment of GAMT deficiency is aimed at supplying the body with creatine and reducing the toxic levels of GAA.^4-6,9-10 The treatment for GAMT deficiency is oral creatine powder to replenish creatine in the brain and ornithine powder to reduce GAA. Creatine and ornithine powders are freely available as over-the-counter powders but not available as tablets or liquid, so each dose must be accurately weighed out. These powders are essential and must be taken typically multiple times a day and life-long. If GAMT deficiency is diagnosed early and treated before symptoms develop, children are more likely to remain healthy and have normal development.^4-7 For children that have developed symptoms of GAMT deficiency, treatment can help improve or stabilise the symptoms.^6,12

Other extra treatments are also sometimes used to help further lower GAA. This may include a low arginine/protein diet and sodium benzoate supplementation, but this may not be suitable for everyone. There are also strategies to manage the symptoms in children who had developed symptoms, such as physiotherapy, occupational therapy, speech therapy, management of seizures and management of the movement disorders.³

Please speak to your medical team to learn more about the possible treatment or management options for your condition. Treatment will depend on an individual’s specific condition and symptoms. It is also important to stay connected to your medical team so that you can be made aware of any upcoming clinical trial opportunities.

Healthcare professionals involved in the care of individuals with GAMT deficiency may include general practitioners (GP), paediatricians, geneticists, metabolic specialists, neurologists, dieticians, occupational therapists, physiotherapists, speech therapists and others. The need for different healthcare professionals may change over a person’s lifetime and extend beyond those listed here.

Clinical care for rare diseases often involves a multidisciplinary team of medical, care and support professionals. Please note that the information provided here is as a guide and that RVA does not necessarily monitor or endorse specific clinics or health experts.

For many rare diseases, palliative care services may be relevant and useful. Palliative care services are available for people (adults, children and their families) living with a life-limiting illness and is not only for end-of-life care. It can also help at any stage of illness from diagnosis onwards, and will look different for different people. Palliative care services provide assistance, support, resources and tools to help people manage their illness and the symptoms, ease pain, and improve comfort and quality of life. If this is relevant to you and you wish to find out more information about palliative care and how it can help you, please visit:

• Australian Institute of Health and Welfare: Palliative care Overview
• Australian Government Department of Health, Disability and Ageing: Palliative care
• Palliative Care Australia

We are not aware of any clinical care guidelines for GAMT deficiency in Australia. If you know of any relevant care guidelines, please let us know via the Contribute page.

The following recommendations is available from international experts outside Australia; however, there may be information that is not relevant or applicable to the Australian context, and may not be up to date:

• Guanidinoacetate methyltransferase (GAMT) deficiency: Outcomes in 48 individuals and recommendations for diagnosis, treatment and monitoring – please note that this was published in 2014 and the information may not be current

Individuals living with rare diseases may have complex medical issues and disabilities, which are not always visible. It is often useful to refer to their medical history as well as personal information such as a medical card, doctor’s letter, or if available, a rare disease passport, for relevant information.

In addition, individuals, their parents, families and carers often develop extensive expertise on their specific rare disease. It is important to recognise that they can contribute valuable knowledge about their rare condition. Rare diseases often impact individuals differently, so it’s important to consider a person’s lived experience.

It may be important to consider the following when managing individuals living with GAMT deficiency at emergency departments/services:

• the main treatment of GAMT deficiency involves use of supplements to supply what the body cannot produce – these are over-the-counter powders that need to be accurately weighed out for each dose and taken orally.

There are specific considerations around participating in rare disease research, including clinical trials. It is important to be mindful of issues such as data privacy, research ethics, consent and differences in research regulations between Australia and other countries. For more information, please visit the RARE Portal’s Considerations for Participating in Health and Medical Research page.

If you are interested in finding clinical trials for your condition, please visit the following websites; however, there may not be any clinical trials available:

• Australian Clinical Trials
• ClinicalTrials.gov

It is best to discuss your interest in research, including clinical trials,  with your medical team to determine suitability and eligibility.

Australian Organisation:
Association for Creatine Deficiencies Australia (ACD Australia)
Website: https://www.acdaustralia.org/

ACD Australia is a not-for-profit organisation dedicated to the three cerebral creatine deficiency syndromes, which includes GAMT deficiency.

Please note that RVA does not monitor or endorse each group/organisation’s operational governance and activities. When engaging with a group, please consider the information on the RARE Portal’s Finding Helpful Peer and Community Supports page.

GAMT deficiency varies between individuals, and each person’s experience is unique.

If you would like to share your personal story with RVA, please visit the Rare Voices Australia: Share Your Story page. RVA will consider your story for publishing on our website and inclusion on the RARE Portal.

For information on available government and social services that provide support for individuals with a rare disease, please visit the National and State Services pages.

People living with a rare disease often face unique challenges such as diagnostic delays, misdiagnoses, limited treatment options, and limited access to rare disease specialists and support. These challenges may impact people’s emotional wellbeing and quality of life. Many find it helpful to seek mental health and wellbeing support to cope with ongoing stress and uncertainty. Connecting with people who have shared experiences through a support group may also be helpful. Information about relevant mental health and wellbeing support can be found at:

• Mental Health and Wellbeing Support for Australians Living with a Rare Disease
• The National and State Services pages underneath the ‘Mental Health’ sections listed

Further information on GAMT deficiency can be found at:

• Genetic and Rare Diseases (GARD) Information Center: Guanidinoacetate methyltransferase deficiency
• National Organization for Rare Disorders (NORD): Guanidinoacetate Methyltransferase Deficiency
• Association for Creatine Deficiencies: GAMT Deficiency Information

GeneReviews®: Creatine Deficiency Disorders

Orphanet: Guanidinoacetate methyltransferase deficiency

Association for Creatine Deficiencies: For Clinicians (United States of America)

This page has been co-developed by Rare Voices Australia (RVA)’s RARE Portal team in consultation with a lived experience expert.

If you are aware of any additional information that may benefit stakeholders with an interest in this page, or if you notice any broken links or inaccurate information, please let us know via the Contribute page.