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Disease Profile

L-2-hydroxyglutaric aciduria

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.
<1 / 1 000 000

< 331

US Estimated

< 514

Europe Estimated

Age of onset

Childhood

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ICD-10

E72.8

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)

L-2-hydroxyglutaric acidemia

Categories

Congenital and Genetic Diseases; Metabolic disorders; Nervous System Diseases

Summary

L-2-hydroxyglutaric aciduria is an inherited metabolic condition that is associated with progressive brain damage. Signs and symptoms of this condition typically begin during infancy or early childhood and may include developmental delay, seizures, speech difficulties, macrocephaly and abnormalities in a part of the brain called the cerebellum, which is involved in coordinating movement (i.e. balance and muscle coordination). L-2-hydroxyglutaric aciduria is caused by changes (mutations) in the L2HGDH gene and is inherited in an autosomal recessive manner.[1][2] Treatment is focused on alleviating the signs and symptoms of the condition, such as medications to control seizures.[3]

Symptoms

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
Encephalitis
Brain inflammation
0002383
Intellectual disability, progressive
Mental retardation, progressive
Progressive mental retardation

[ more ]

0006887
Intellectual disability, severe
Early and severe mental retardation
Mental retardation, severe
Severe mental retardation

[ more ]

0010864
Seizure
0001250
30%-79% of people have these symptoms
Abnormality of extrapyramidal motor function
0002071
Aplasia/Hypoplasia of the cerebellum
Absent/small cerebellum
Absent/underdeveloped cerebellum

[ more ]

0007360
Behavioral abnormality
Behavioral changes
Behavioral disorders
Behavioral disturbances
Behavioral problems
Behavioral/psychiatric abnormalities
Behavioural/Psychiatric abnormality
Psychiatric disorders
Psychiatric disturbances

[ more ]

0000708
Macrocephaly
Increased size of skull
Large head
Large head circumference

[ more ]

0000256
Muscular hypotonia
Low or weak muscle tone
0001252
Neoplasm of the nervous system
Tumor of the nervous system
0004375
Spastic tetraparesis
0001285
5%-29% of people have these symptoms
Dysphasia
0002357
Percent of people who have these symptoms is not available through HPO
Abnormal pyramidal sign
0007256
Autosomal recessive inheritance
0000007
Cerebellar atrophy
Degeneration of cerebellum
0001272
Corpus callosum atrophy
0007371
Developmental regression
Loss of developmental milestones
Mental deterioration in childhood

[ more ]

0002376
Gliosis
0002171
Global brain atrophy
Generalized brain degeneration
0002283
Hearing impairment
Deafness
Hearing defect

[ more ]

0000365
Infantile onset
Onset in first year of life
Onset in infancy

[ more ]

0003593
L-2-hydroxyglutaric acidemia
0040147
L-2-hydroxyglutaric aciduria
0040144
Leukoencephalopathy
0002352
Morphological abnormality of the pyramidal tract
0002062
Nystagmus
Involuntary, rapid, rhythmic eye movements
0000639
Optic atrophy
0000648
Severe demyelination of the white matter
0007258
Strabismus
Cross-eyed
Squint
Squint eyes

[ more ]

0000486

Diagnosis

Making a diagnosis for a genetic or rare disease can often be challenging. Healthcare professionals typically look at a person’s medical history, symptoms, physical exam, and laboratory test results in order to make a diagnosis. The following resources provide information relating to diagnosis and testing for this condition. If you have questions about getting a diagnosis, you should contact a healthcare professional.

Testing Resources

  • The Genetic Testing Registry (GTR) provides information about the genetic tests for this condition. The intended audience for the GTR is health care providers and researchers. Patients and consumers with specific questions about a genetic test should contact a health care provider or a genetics professional.

    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 L-2-hydroxyglutaric aciduria. This website is maintained by the National Library of Medicine.

          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 L-2-hydroxyglutaric aciduria. Click on the link to view a sample search on this topic.

            References

            1. 2-hydroxyglutaric aciduria. Genetics Home Reference. August 2013; https://ghr.nlm.nih.gov/condition/2-hydroxyglutaric-aciduria.
            2. L-2-hydroxyglutaric aciduria. OMIM. July 2015; https://www.omim.org/entry/236792.
            3. L-2-hydroxyglutaric aciduria. Orphanet. May 2012; https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=en&Expert=79314.