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Disease Profile
Dihydrolipoamide dehydrogenase deficiency
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.
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Age of onset
Childhood
ICD-10
E74.4
Inheritance
Autosomal dominant A pathogenic variant in only one gene copy in each cell is sufficient to cause an autosomal dominant disease.
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.
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.
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.
X-linked
recessive Pathogenic variants in both copies of a gene on the X chromosome cause an X-linked recessive disorder.
recessive Pathogenic variants in both copies of a gene on the X chromosome cause an X-linked recessive disorder.
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.
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.
Not applicable
Other names (AKA)
Pyruvate dehydrogenase E3 deficiency; DLD deficiency; E3-deficient maple syrup urine disease;
Categories
Congenital and Genetic Diseases; Metabolic disorders; Nervous System Diseases
Summary
Dihydrolipoamide dehydrogenase (DLD) deficiency is a very rare condition that can vary in age of onset, symptoms and severity. The condition may be characterized by early-onset lactic acidosis and delayed development (most commonly); later-onset neurological dysfunction; or adult-onset isolated liver disease. Signs and symptoms may include lactic acidosis shortly after birth;
Symptoms
Isolated liver involvement, which can range from hepatomegaly (enlarged liver) to life-threatening liver failure, can also occur in the newborn period, or as late as the 3rd decade of life. A few people with DLD deficiency have become affected later in childhood with ataxia and
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 | ||
Generalized hypotonia |
Decreased muscle tone
Low muscle tone
[ more ] |
0001290 |
Global |
0001263 | |
Increased serum lactate | 0002151 | |
Lactic acidosis |
Increased lactate in body
|
0003128 |
Neurodevelopmental delay | 0012758 | |
Vomiting |
Throwing up
|
0002013 |
30%-79% of people have these symptoms | ||
Elevated hepatic transaminase |
High liver enzymes
|
0002910 |
Elevated plasma branched chain |
0008344 | |
Feeding difficulties |
Feeding problems
Poor feeding
[ more ] |
0011968 |
Hepatic |
0002480 | |
Hepatomegaly |
Enlarged liver
|
0002240 |
Hypercoagulability | 0100724 | |
Low blood sugar
|
0001943 | |
Increased urine alpha-ketoglutarate concentration | 0012402 | |
Lethargy | 0001254 | |
Seizure | 0001250 | |
Spasticity |
Involuntary muscle stiffness, contraction, or spasm
|
0001257 |
5%-29% of people have these symptoms | ||
Abnormal cardiac ventricular function | 0030872 | |
Ataxia | 0001251 | |
Behavioral abnormality |
Behavioral changes
Behavioral disorders
Behavioral disturbances
Behavioral problems
Behavioral/psychiatric abnormalities
Behavioural/Psychiatric abnormality
Psychiatric disorders
Psychiatric disturbances
[ more ] |
0000708 |
Cardiomyopathy |
Disease of the heart muscle
|
0001638 |
Decreased liver function |
Liver dysfunction
|
0001410 |
Decreased plasma carnitine | 0003234 | |
Failure to thrive |
Faltering weight
Weight faltering
[ more ] |
0001508 |
Hepatic failure |
Liver failure
|
0001399 |
Hyperammonemia |
High blood ammonia levels
|
0001987 |
Hyperisoleucinemia |
High blood isoleucine concentration
|
0010913 |
Abnormally small skull
Decreased circumference of cranium
Decreased size of skull
Reduced head circumference
Small head circumference
[ more ] |
0000252 | |
Muscle spasm | 0003394 | |
Reduced visual acuity |
Decreased clarity of vision
|
0007663 |
Percent of people who have these symptoms is not available through HPO | ||
0000007 | ||
Dystonia | 0001332 | |
Encephalopathy | 0001298 | |
Hypertrophic cardiomyopathy |
Enlarged and thickened heart muscle
|
0001639 |
Metabolic acidosis | 0001942 | |
0003828 |
Cause
Mutations in the DLD gene impair the function of DLD, preventing the 3 enzyme complexes from functioning properly. This causes a build-up of
Treatment
Unfortunately, the treatments that have been attempted in children with the early-onset neurologic form do not appear to significantly alter the course of the disease. Even with treatment, children often do not survive infancy or have varying degrees of chronic neurologic impairment if they survive the initial episode. Depending on individual enzyme complex deficiencies, treatment may involve certain dietary restrictions or certain diets; use of medical foods; and/or supplementation of specific
There is limited data for the chronic management of people with the primarily hepatic (liver-related) form of the disease. Management typically involves supportive therapy during times of acute liver injury or failure, and may include nutritional support; IV glucose for
More detailed information about the management of DLD deficiency can be viewed on the GeneReviews Web site. GeneReviews is intended for use by genetics professionals. Those not familiar with the principles discussed on the GeneReviews Web site are encouraged to speak with a genetics professional or other healthcare provider regarding information of interest.
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 Dihydrolipoamide dehydrogenase deficiency. This website is maintained by the National Library of Medicine.
In-Depth Information
- GeneReviews provides current, expert-authored, peer-reviewed, full-text articles describing the application of genetic testing to the diagnosis, management, and genetic counseling of patients with specific inherited conditions.
- 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 Dihydrolipoamide dehydrogenase deficiency. Click on the link to view a sample search on this topic.
References
- Shane C Quinonez and Jess G Thoene. Dihydrolipoamide Dehydrogenase Deficiency. GeneReviews. July 17, 2014; https://www.ncbi.nlm.nih.gov/books/NBK220444/.
- Dihydrolipoamide dehydrogenase deficiency. Genetics Home Reference. September, 2014; https://ghr.nlm.nih.gov/condition/dihydrolipoamide-dehydrogenase-deficiency.
- Brown G. Pyruvate dehydrogenase E3 deficiency. Orphanet. April, 2012; https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=en&Expert=2394.
- Shane C. Quinonez, Steven M. Leber, Donna M. Martin, Jess G. Thoene, and Jirair K. Bedoyan. Leigh syndrome in a girl with a novel DLD mutation causing E3 deficiency. Pediatr Neurol. January, 2013; 48(1):67-72.
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