Glutaric acidaemia type I is a genetic, neurometabolic condition (metabolic condition that affects the brain).¹ It is an organic acid disorder (where the body is unable to break down protein building blocks, leading to build up of harmful organic acids).^2,3 People with glutaric acidaemia type I are not able to properly break down certain amino acids (protein building block), in particular lysine (an amino acid found in many foods). This incomplete breakdown of lysine causes build-up of certain substances (such as glutaric acid (GA), 3-hydroxyglutaric acid (3-OH-GA), glutaconic acid and glutarylcarnitine) in the body.^1,2 These substances (except for glutarylcarnitine) are toxic to the brain.²

Symptoms of glutaric acidaemia type I are often not very obvious at birth. Babies may not have any symptoms (asymptomatic) or they may be born with low muscle tone (hypotonia) or abnormally large head size (macrocephaly).^1,2 If the condition is not diagnosed and treated early, acute encephalopathic crisis (a sudden episode that affects the brain and disrupts brain function) may occur, usually in the first few years of life; this may be precipitated by (made to occur earlier than it would have) by a fever or infection. This can cause damage to the brain (brain injury), causing dystonia (where movement is affected), loss of motor skills, seizures and other issues. Some children may also develop brain injury even without an identified encephalopathic crisis.^2,4 In some cases, there may also be subdural hemorrhage (bleeding around the brain) and retinal hemorrhage (bleeding within the retina layer in the eyes), affecting brain function and causing vision issues.^1-3

In Australia, glutaric acidaemia type I is often detected shortly after birth via newborn bloodspot screening (NBS) programs. Additional testing is required to confirm the diagnosis. For individuals who are not screened at birth, glutaric acidaemia type I is often diagnosed after symptoms develop. Early detection and management of glutaric acidaemia type I is important to reduce the risk of encephalopathic crises and brain injury, and improve outcomes.^2,4

Synonyms:¹ GA1; GCDHD; Glutaric acidemia type 1; Glutaric aciduria type 1; Glutaryl-coenzyme A dehydrogenase deficiency; Glutaryl-CoA dehydrogenase deficiency

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:25 Glutaryl-CoA dehydrogenase deficiency

ICD-11: 5C50.E1 Cerebral organic aciduria

Symptoms of glutaric acidaemia type I can vary widely between individuals.⁴ Some individuals may be severely affected whilst others may have no symptoms (asymptomatic) or are mildly affected.^2,4 

Many babies with glutaric acidaemia type I are born with low muscle tone (hypotonia) or abnormally large head size (macrocephaly).^1,2  If glutaric acidaemia type I is not diagnosed early and treated appropriately in a timely manner, acute encephalopathic crisis (a sudden episode that affects the brain and disrupts brain function) can occur from around three months to three years of life, often triggered by an infection, fever or fasting, and cause damage to the brain. Some children may also develop brain injury even without an identified encephalopathic crisis.^2,4  The brain injury can result in irreversible dystonia (where movement is affected), loss of motor skills, and seizures.⁴ In severe cases, it can progress to status dystonicus (a severe life-threatening episode of dystonia) and result in early death.⁵  In some cases, there may also be subdural hemorrhage (bleeding around the brain) and retinal hemorrhage (bleeding within the retina layer in the eyes), affecting brain function and causing vision issues .^1-3 Early diagnosis and appropriate  management can help prevent or reduce the risk of brain injury and its resulting complications.⁴ 

For some individuals, symptoms may develop gradually over time (known as the insidious or late onset) from 6 years of age onwards.^2,4 Symptoms may be similar to cerebral palsy symptoms and may also include epilepsy and stroke.⁴

There may also be further complications, such as chronic kidney disease, during adolescence and adulthood, even with treatment.^2,4,5

Please speak to your medical team to learn more about the symptoms of this condition.

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.

Glutaric acidaemia type I is a genetic condition. It is caused by disease-causing genetic changes (variants) in the GCDH gene on Chromosome 19.¹ The GCDH gene is responsible for producing the glutaryl-CoA dehydrogenase (GCDH) enzyme.

All individuals have two copies (alleles) of the GCDH gene – one copy inherited from each parent. Glutaric acidaemia type I is an autosomal recessive condition,¹ which means both copies of the GCDH 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

Newborn screening

In Australia, glutaric acidaemia type I is usually detected via the newborn bloodspot screening (NBS) programs.  Shortly after birth and with parental consent, a nurse or midwife will collect the baby’s blood via a heel prick blood test. The healthcare provider will then send it to a specific laboratory to test for a range of rare conditions, including glutaric acidaemia type I. If the test results suggest that there is a risk of the baby having one of the screened conditions, laboratory staff will promptly get in touch with healthcare providers. The healthcare providers will then arrange for the baby to have further testing to confirm if the baby actually has the condition. The healthcare providers will also organise for the baby to receive urgent care if required. Depending on your state or territory, parents may or may not receive a notification if the test results are clear. You can find out more about NBS in your state or territory at Australian Government Department of Health, Disability and Ageing: Delivering newborn bloodspot screening programs.

Newborn bloodspot screening is a reliable way to check for certain rare conditions early in life. Although it’s extremely rare, cases can sometimes be missed. If you are concerned your baby may have a condition that they have already been screened for, you should contact a medical professional.

Diagnosis

A diagnosis of glutaric acidaemia type I may be suspected based on an abnormal result from NBS but additional tests or a clinical examination will be required to confirm a diagnosis. For individuals who are not screened at birth, glutaric acidaemia type I is often diagnosed after symptoms develop.

Diagnosis of glutaric acidaemia type I may be made based on clinical evaluation of symptoms, brain imaging, laboratory tests on blood and urine samples to detect for increased levels of specific metabolites (such as glutarylcarnitine (C5DC), glutaric acid and 3-hydroxyglutaric acid) and confirmed by genetic testing or in some cases, analyses of enzyme activity.^1,4

As part of the diagnostic process, doctors may do a differential diagnosis, which is to rule out other conditions that have similar symptoms, such as Reye’s syndrome, familial infantile bilateral striatal necrosis, familial megalencephaly, encephalitis, post-encephalitic Parkinsonism, dystonic cerebral palsy, abusive head trauma (battered child syndrome) with chronic subdural effusions (as symptoms of GA1 may include subdural and retinal hemorrhage), sudden infant death syndrome (SIDS), suspected vaccine induced brain-injury, Leigh syndrome, Canavan disease, Glutaric acidaemia type 2, isolated methylmalonic acidemia, propionic acidemia and glutaric acidemia type 3.^1,4

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

There is currently no curative treatment for glutaric acidaemia type I; however, early diagnosis and appropriate management can help prevent or reduce the risk of brain injury and its resulting complications, and can improve overall outcomes for individuals with glutaric acidaemia type I.⁴ Early diagnosis and treatment is crucial as the complications of brain injury is often irreversible; if treatment is only commenced after brain injury, the treatment may prevent further progression for some individuals.⁵

Management of glutaric acidaemia type I involves a long-term low lysine diet and a special nutritional supplement, as well as carnitine supplementation.^1,2,4-6 There should be prompt emergency treatment during times of illness or fasting to manage the risk of acute encephalopathic crisis. More information about recommended emergency treatment can be found at Recommendations for diagnosing and managing individuals with glutaric aciduria type 1: Third revision.

Management of symptoms may include management of movement disorders and seizures, feeding therapy, physiotherapy, occupational therapy, speech therapy and use of mobility and medical aids.⁴

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. For many rare diseases, treatment options may be limited. Participation in a clinical trial may provide access to new or emerging therapies.

Healthcare professionals involved in the clinical care of individuals with glutaric acidaemia type I may include general practitioners (GP), paediatricians, metabolic physicians, genetic counsellors, neurologists, metabolic dieticians, metabolic nurses, physiotherapists, occupational therapists, speech therapists, psychologists and other health care professionals trained to look after metabolic disorders. The need for different healthcare professionals may change over a person’s lifetime and extend beyond those listed here.  It is recommended that care be managed by a metabolic specialist team.⁴

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.

This may not be applicable to all rare diseases but for many, 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

If you know of any relevant clinical care guidelines, please let us know via the  Contribute page.

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

Recommendations for diagnosing and managing individuals with glutaric aciduria type 1: Third revision was published in 2023; development of this revision involved participation of 23 international experts in metabolic medicine, child neurology, clinical biochemistry, genetics, nutrition, (neuro-)radiology and psychology as well as 13 professional societies as well as a representative of a patient support group.

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.

Below are some considerations for the emergency management of individuals living with glutaric acidaemia type I, including when presenting to emergency departments:⁴

• individuals are at risk of acute encephalopathic crisis, particularly during times of illness and fasting. Emergency treatment will be required and a metabolic specialist team should be consulted.

The following resources has information about emergency treatment, including inpatient and outpatient emergency treatment:

• Recommendations for diagnosing and managing individuals with glutaric aciduria type 1: Third revision 
• GeneReviews^®: Glutaric Acidemia Type 1

Metabolic Dietary Disorders Association (MDDA): Latest Research Updates has information about key areas of ongoing research for various inborn errors of metabolism conditions, including organic acidemias.

Australian Organisation:

Metabolic Dietary Disorders Association (MDDA)
Website: https://mdda.org.au/

Metabolic Dietary Disorders Association Inc (MDDA) is the national peak consumer body dedicated to supporting, educating, connecting, and representing all individuals their families and carers living with Inborn Errors of protein Metabolism (IEpM).

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.

Glutaric aciduria type I 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.

The ASIEM Low Protein Handbook for Organic acid disorders

Organic Aciduria Fruit and Veg Counting Lists

Organic Aciduria General Protein Counting Lists

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 relevant to glutaric aciduria type I can be found at:

• Metabolic Dietary Disorders Association (MDDA): Glutaric Acidaemia Type 1
• Genetic and Rare Diseases (GARD) Information Center: Glutaryl-coa dehydrogenase deficiency
• National Organization for Rare Disorders (NORD): Glutaric Aciduria Type I

Orphanet: Glutaryl-CoA dehydrogenase deficiency

Online Mendelian Inheritance in Man, OMIM^®: #231670 – Glutaric acidemia 1; GA1

This page has been developed by Rare Voices Australia (RVA)’s RARE Portal team. 

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.