Glutaric acidemia type I

Title

Other Names:

Glutaric acidemia type 1; Glutaric acidemia 1; Glutaric aciduria 1; Glutaric acidemia type 1; Glutaric acidemia 1; Glutaric aciduria 1; GA 1; Glutaryl-CoA dehydrogenase deficiency See More

Categories:

Congenital and Genetic Diseases; Metabolic disorders; Nervous System Diseases; Congenital and Genetic Diseases; Metabolic disorders; Nervous System Diseases; Newborn Screening See More

Summary Summary

Glutaric acidemia type I (GA1) is a genetic metabolic disorder. People with GA1 don't make enough of one of the enzymes needed to break down certain amino acids found in the proteins we eat. Without enough of the enzyme, the breakdown products of these amino acids build up in tissues of the body. The buildup of these chemicals can damage the brain, especially the area of the brain called the basal ganglia. The basal ganglia helps control the body's movements.^[1]^[2]

Without treatment, newborns with GA1 may at first not have any symptoms other than possibly having a slightly large head. Some, however, may have weak muscles and early signs of developmental delay. For most children with GA1, if untreated, an infection or fever will trigger an episode that causes serious damage to the basal ganglia. In some children, the brain damage will happen without a triggering fever. Damage to the basal ganglia will make it hard for the child to control the movements of their body. The damage cannot be reversed. However if treatment is started in a newborn with GA1 before symptoms begin, 80-90% of people with GA1 will not develop symptoms. Treatment however must be followed strictly, especially for the first six years of life. Treatment includes a low-lysine diet, carnitine supplementaion, and emergency treatment during an fever or acute episode.^[1]^[2]

GA1 is caused by mutations in the GCDH gene and is inherited in an autosomal recessive manner. GA1 is included on the newborn screening panel in most countries.^[1]^[2]

Last updated: 4/18/2017

Symptoms Symptoms

If treatment is started as a newborn before symptoms begin, 80-90% of people with glutaric acidemia type 1 (GA1) will not develop any symptoms. However, if treatment is not started early or is not followed properly, the severity of symptoms varies from person to person. Symptoms usually begin in infancy or early childhood, but sometimes symptoms begin in adolescence or adulthood. In rare cases, a person with GA1 does not develop any symptoms, even if not treated.^[1]^[2]

Many newborns with GA1 have a large head circumference (macrocephaly), but may not have any other symptom. About half will have weak muscle tone (hypotonia) and early signs of developmental delay. If GA1 is untreated, an infection or fever will usually trigger an acute episode that causes serious damage to the basal ganglia. The basal ganglia is the area of the brain that helps control movement. In some children, the brain damage will happen without a triggering fever. Damage to the basal ganglia, especially before the age of 6 years old, can cause a complex movement disorder, similar to cerebral palsy. Controlling the movement of hands, arms, feet, legs, head, and neck may become very hard. Movements may be jerky or rigid. Muscle spasms may occur. Repeated stress on the body (such as infection and fever) can cause symptoms to worsen. Some studies have shown that the intellectual ability of a person with GA1, even if untreated, is not affected. Others report that although not common, mild to moderate intellectual disabilities may occur in some untreated children.^[1]^[2]

Last updated: 4/18/2017

This table lists symptoms that people with this disease may have. For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed. This information comes from a database called the Human Phenotype Ontology (HPO) . The HPO collects information on symptoms that have been described in medical resources. The HPO is updated regularly. Use the HPO ID to access more in-depth information about a symptom.

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Medical Terms	Other Names	Learn More: HPO ID
80%-99% of people have these symptoms
Abnormal enzyme/coenzyme activity		0012379
Glutaric aciduria		0003150
30%-79% of people have these symptoms
Abnormal caudate nucleus morphology		0002339
Abnormal putamen morphology		0031982
Athetosis	Involuntary writhing movements in fingers, hands, toes, and feet	0002305
Communicating hydrocephalus		0001334
Dysarthria	Difficulty articulating speech	0001260
Dysphagia	Poor swallowing Swallowing difficulties Swallowing difficulty [ more ]	0002015
Feeding difficulties	Feeding problems Poor feeding [ more ]	0011968
Headache	Headaches	0002315
Open operculum		0100954
Pallidal degeneration		0007132
Poor motor coordination		0002275
Progressive macrocephaly	Progressively abnormally enlarging cranium Progressively abnormally enlarging skull [ more ]	0004481
Subependymal nodules		0009716
T2 hypointense basal ganglia		0012753
Widened subarachnoid space		0012704
5%-29% of people have these symptoms
Abnormality of the cerebral white matter		0002500
Abnormality of the respiratory system		0002086
Ataxia		0001251
Chorea		0002072
Dementia	Dementia, progressive Progressive dementia [ more ]	0000726
Developmental regression	Loss of developmental milestones Mental deterioration in childhood [ more ]	0002376
Exercise intolerance	Decreased ability to exercise Inability to exercise [ more ]	0003546
Fasting hypoglycemia	Low blood sugar when fasting	0003162
Infantile spasms		0012469
Joint dislocation	Joint dislocations Recurrent joint dislocations [ more ]	0001373
Limb dystonia		0002451
Loss of consciousness	Passing out	0007185
Retinal hemorrhage	Retinal bleeding	0000573
Rigidity	Muscle rigidity	0002063
Seizure		0001250
Severe muscular hypotonia	Severely decreased muscle tone	0006829
Subdural hemorrhage		0100309
Tremor		0001337
Ventriculomegaly		0002119
Vertigo	Dizzy spell	0002321
1%-4% of people have these symptoms
Chronic kidney disease		0012622
Peripheral neuropathy		0009830
Percent of people who have these symptoms is not available through HPO
Autosomal recessive inheritance		0000007
Choreoathetosis		0001266
Delayed myelination		0012448
Dilation of lateral ventricles		0006956
Dystonia		0001332
Elevated circulating glutaric acid concentration		0003530
Failure to thrive	Faltering weight Weight faltering [ more ]	0001508
Generalized hypotonia	Decreased muscle tone Low muscle tone [ more ]	0001290
Hepatomegaly	Enlarged liver	0002240
Hyperketonemia	Increased level of ketone bodies in blood	0410175
Hypoglycemia	Low blood sugar	0001943
Infantile encephalopathy		0007105
Ketonuria		0002919
Macrocephaly	Increased size of skull Large head Large head circumference [ more ]	0000256
Metabolic acidosis		0001942
Muscular hypotonia	Low or weak muscle tone	0001252
Opisthotonus		0002179
Spastic diplegia		0001264
Symmetrical progressive peripheral demyelination		0006873

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Last updated: 11/1/2020

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Inheritance Inheritance

Glutaric acidemia type I (GA1) can be passed down in families. This is because GA1 is caused by changes or mutations in the GCDH gene.^[1] Like most genes, the GCDH gene comes in a pair (two copies). One copy comes from the mother and one copy from the father. In order to have GA1, both copies of the GCDH gene must have a mutation. This means that GA1 is an autosomal recessive disorder.^[3] A person with a mutation in only one copy of the GCDH gene is called a carrier. Carriers of an autosomal recessive disease like GA1 usually have no signs or symptoms.

When 2 carriers of GA1 have children, each child has a:

25% chance of having GA1
50% chance to be a carrier of GA1 like each parent
25% chance of not having GA1 and not being a carrier of GA1 (in other words, having two normal copies of the gene)

If a person with GA1 and a carrier of GA1 have children, each child has a:

50% chance of having GA1
50% chance of being a carrier

If a person with GA1 and a person who has two normal copies of the GCDH gene have children, each child will be a carrier of GA1.

Last updated: 4/18/2017

Diagnosis Diagnosis

The Genetic Testing Registry (GTR) provides information about the labs that offer genetic testing for this condition. The intended audience for the GTR is health care providers and researchers. Therefore, patients and consumers with specific questions about a genetic test should contact a health care provider or a genetics professional.

Last updated: 4/29/2015

Newborn Screening

An ACTion (ACT) sheet is available for this condition that describes the short-term actions a health professional should follow when an infant has a positive newborn screening result. ACT sheets were developed by experts in collaboration with the American College of Medical Genetics.
An Algorithm flowchart is available for this condition for determining the final diagnosis in an infant with a positive newborn screening result. Algorithms are developed by experts in collaboration with the American College of Medical Genetics.
Baby's First Test is the nation's newborn screening education center for families and providers. This site provides information and resources about screening at the local, state, and national levels and serves as the Clearinghouse for newborn screening information.
The Newborn Screening Coding and Terminology Guide has information on the standard codes used for newborn screening tests. Using these standards helps compare data across different laboratories. This resource was created by the National Library of Medicine.
National Newborn Screening and Global Resource Center (NNSGRC) provides information and resources in the area of newborn screening and genetics to benefit health professionals, the public health community, consumers and government officials.

Treatment Treatment

The resources below provide information about treatment options for this condition. If you have questions about which treatment is right for you, talk to your healthcare professional.

Management Guidelines

Orphanet Emergency Guidelines is an article which is expert-authored and peer-reviewed that is intended to guide health care professionals in emergency situations involving this condition.

Prognosis Prognosis

Glutaric acidemia type 1 (GA1) is a treatable disorder. If treatment begins in the newborn period before symptoms begin, and the treatment is followed properly, children with GA1 usually grow and develop normally. However, since newborn screening for GA1 (allowing treatment to begin before symptoms) only began in the 1990s, it is not yet known if GA1 may cause complications later in life.^[1]^[2]

If not promptly and properly treated, GA1 usually causes serious, irreversible, neurologic damage. The damage mainly affects control of voluntary muscle movement. The overall impact of GA1 on a person's life will depend on the amount of damage to the brain, but can be severe. In general, a person with GA1 who has an acute brain damaging episode before the age of 6 years old is at increased risk for medical problems throughout their life, and their life expectancy is shortened.^[1]^[2]

Last updated: 4/18/2017

Find a Specialist Find a Specialist

If you need medical advice, you can look for doctors or other healthcare professionals who have experience with this disease. You may find these specialists through advocacy organizations, clinical trials, or articles published in medical journals. You may also want to contact a university or tertiary medical center in your area, because these centers tend to see more complex cases and have the latest technology and treatments.

If you can’t find a specialist in your local area, try contacting national or international specialists. They may be able to refer you to someone they know through conferences or research efforts. Some specialists may be willing to consult with you or your local doctors over the phone or by email if you can't travel to them for care.

You can find more tips in our guide, How to Find a Disease Specialist. We also encourage you to explore the rest of this page to find resources that can help you find specialists.

Healthcare Resources

To find a medical professional who specializes in genetics, you can ask your doctor for a referral or you can search for one yourself. Online directories are provided by the American College of Medical Genetics and the National Society of Genetic Counselors. If you need additional help, contact a GARD Information Specialist. You can also learn more about genetic consultations from Genetics Home Reference.

Related Diseases Related Diseases

Related diseases are conditions that have similar signs and symptoms. A health care provider may consider these conditions in the table below when making a diagnosis. Please note that the table may not include all the possible conditions related to this disease.

Conditions with similar signs and symptoms from Orphanet
GDD is often misdiagnosed. Differential diagnosis includes encephalitis, Reye's syndrome, familial infantile bilateral striatal necrosis, familial megalencephaly, postencephalitic Parkinsonism (see these terms), dystonic cerebral palsy, battered child syndrome with chronic subdural effusions, sudden infant death syndrome and vaccine induced brain-injury. Visit the Orphanet disease page for more information.

Conditions with similar signs and symptoms from Orphanet

GDD is often misdiagnosed. Differential diagnosis includes encephalitis, Reye's syndrome, familial infantile bilateral striatal necrosis, familial megalencephaly, postencephalitic Parkinsonism (see these terms), dystonic cerebral palsy, battered child syndrome with chronic subdural effusions, sudden infant death syndrome and vaccine induced brain-injury.

Visit the Orphanet disease page for more information.

Organizations Organizations

Support and advocacy groups can help you connect with other patients and families, and they can provide valuable services. Many develop patient-centered information and are the driving force behind research for better treatments and possible cures. They can direct you to research, resources, and services. Many organizations also have experts who serve as medical advisors or provide lists of doctors/clinics. Visit the group’s website or contact them to learn about the services they offer. Inclusion on this list is not an endorsement by GARD.

Organizations Supporting this Disease

Genetic Metabolic Dietitians International
P.O. Box 1462
Hillsborough, NC 27278
E-mail: info@gdmi.org
Website: http://www.gmdi.org/
Metabolic Support UK
5 Hilliards Court
Sandpiper Way
Chester Business Park
Chester, CH4 9QP United Kingdom
Toll-free: 0800 652 3181
Telephone: 0845 241 2173
E-mail: https://www.metabolicsupportuk.org/contact-us
Website: https://www.metabolicsupportuk.org
Organic Acidemia Association
9040 Duluth Street
Golden Valley, MN 55427
Telephone: 763-559-1797
Fax: 866-539-4060
E-mail: mkstagni@gmail.com
Website: http://www.oaanews.org/

Organizations Providing General Support

Alex The Leukodystrophy Charity (Alex TLC)
45 Peckham High Street
London, SE15 5EB United Kingdom
Telephone: 020 7701 4388
E-mail: info@alextlc.org
Website: https://www.alextlc.org

Do you know of an organization? We want to hear from you.

Learn More Learn More

These resources provide more information about this condition or associated symptoms. The in-depth resources contain medical and scientific language that may be hard to understand. You may want to review these resources with a medical professional.

Where to Start

Genetics Home Reference (GHR) contains information on Glutaric acidemia type I. This website is maintained by the National Library of Medicine.
The National Organization for Rare Disorders (NORD) has a report for patients and families about this condition. NORD is a patient advocacy organization for individuals with rare diseases and the organizations that serve them.
The Screening, Technology And Research in Genetics (STAR-G) Project has a fact sheet on this condition, which was written specifically for families that have received a diagnosis as a result of newborn screening. This fact sheet provides general information about the condition and answers questions that are of particular concern to parents.

In-Depth Information

The Monarch Initiative brings together data about this condition from humans and other species to help physicians and biomedical researchers. Monarch’s tools are designed to make it easier to compare the signs and symptoms (phenotypes) of different diseases and discover common features. This initiative is a collaboration between several academic institutions across the world and is funded by the National Institutes of Health. Visit the website to explore the biology of this condition.
Online Mendelian Inheritance in Man (OMIM) is a catalog of human genes and genetic disorders. Each entry has a summary of related medical articles. It is meant for health care professionals and researchers. OMIM is maintained by Johns Hopkins University School of Medicine.
Orphanet is a European reference portal for information on rare diseases and orphan drugs. Access to this database is free of charge.
PubMed is a searchable database of medical literature and lists journal articles that discuss Glutaric acidemia type I. Click on the link to view a sample search on this topic.

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GARD Answers GARD Answers

Questions sent to GARD may be posted here if the information could be helpful to others. We remove all identifying information when posting a question to protect your privacy. If you do not want your question posted, please let us know. Submit a new question

My husband is a carrier of glutamic acidemia type I. I am not a carrier. Are our children at risk to develop this condition? Are all individuals with glutaric acidemia identified in infancy? Where can I access genetic testing for glutaminc acidemia type I? See answer

Have a question? Contact a GARD Information Specialist.

References References

Boy N, Mühlhausen C, Maier EM, et al. Proposed recommendations for diagnosing and managing individuals with glutaric aciduria type I: second revision. J Inherit Metab Dis. January 2017; 40(1):75-101. https://www.ncbi.nlm.nih.gov/pubmed/27853989.
Mosaeilhy A, Mohamed MM, C GP, El Abd HS, Gamal R, Zaki OK, Zayed H. Genotype-phenotype correlation in 18 Egyptian patients with glutaric acidemia type I. Metab Brain Dis. April 7 2017; [Epub ahead of print]:https://www.ncbi.nlm.nih.gov/pubmed/28389991.
Glutaric acidemia type I. Genetics Home Reference (GHR). March, 2007; http://www.ghr.nlm.nih.gov/condition/glutaric-acidemia-type-i.

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