Disease Profile

Glutaric acidemia type I

Prevalence ?
Prevalence estimates on Rare Medical Network websites are calculated based on data available from numerous sources, including US and European government statistics, the NIH, Orphanet, and published epidemiologic studies. Rare disease population data is recognized to be highly variable, and based on a wide variety of source data and methodologies, so the prevalence data on this site should be assumed to be estimated and cannot be considered to be absolutely correct.

Unknown

Age of Onset

Infancy

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ICD-10

E72.3

Inheritance

Autosomal dominant ?A pathogenic variant in only one gene copy in each cell is sufficient to cause an autosomal dominant disease

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Autosomal recessive ?Pathogenic variants in both copies of each gene of the chromosome are needed to cause an autosomal recessive disease and observe the mutant phenotype

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X-linked dominant ?X-linked dominant inheritance, sometimes referred to as X-linked dominance, is a mode of genetic inheritance by which a dominant gene is carried on the X chromosome.

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X-linked recessive ?Pathogenic variants in both copies of a gene on the X chromosome cause an X-linked recessive disorder

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Mitochondrial or multigenic ?Mitochondrial genetic disorders can be caused by changes (mutations) in either the mitochondrial DNA or nuclear DNA that lead to dysfunction of the mitochondria and inadequate production of energy.

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Multigenic or multifactor ?Inheritance involving many factors, of which at least one is genetic but none is of overwhelming importance, as in the causation of a disease by multiple genetic and environmental factors.

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Not applicable

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Other Names (AKA)

Glutaric acidemia type 1; Glutaric acidemia 1; Glutaric aciduria 1;

Categories

Congenital and Genetic Diseases; Metabolic disorders; Nervous System Diseases;

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]

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]

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.

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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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.

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

    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.

      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

        Organizations Providing General Support

          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.

              References

              1. 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.
              2. 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.
              3. Glutaric acidemia type I. Genetics Home Reference (GHR). March, 2007; https://www.ghr.nlm.nih.gov/condition/glutaric-acidemia-type-i.