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Disease Profile
Pyruvate dehydrogenase complex 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.
Unknown
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 deficiency; PDHC; PDH;
Categories
Metabolic disorders
Summary
Pyruvate dehydrogenase complex (PDC) deficiency is a type of
The most common form of PDC deficiency is caused by genetic changes (
Symptoms
Most commonly, babies with PDC deficiency develop symptoms soon after birth. Babies may have high levels of lactate in the bloodstream (lactic acidosis). Some babies with severe lactic acidosis may have high levels of ammonia in the blood (hyperammonemia). Other symptoms of PDC deficiency can include having low muscle tone (
There is a wide range of severity of symptoms associated with PDC deficiency. In some cases, the disease is less severe, and episodes of lactic acidosis only occur when a person is ill, under stress, or eats a high amount of carbohydrates. In these situations, signs of lactic acidosis may include abnormal muscle movements (
PDC deficiency affects both males and females. However, males are more likely to have severe forms of the disease than females.[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 | |||
Feeding difficulties in infancy | 0008872 | ||
Lethargy | 0001254 | ||
Muscular hypotonia |
Low or weak muscle tone
|
0001252 | |
30%-79% of people have these symptoms | |||
Abnormal pyramidal sign | 0007256 | ||
Abnormality of eye movement |
Abnormal eye movement
Abnormal eye movements
Eye movement abnormalities
Eye movement issue
[ more ] |
0000496 | |
Aplasia/Hypoplasia of the |
0007370 | ||
Ataxia | 0001251 | ||
Choreoathetosis | 0001266 | ||
Difficulty articulating speech
|
0001260 | ||
Gait disturbance |
Abnormal gait
Abnormal walk
Impaired gait
[ more ] |
0001288 | |
Global |
0001263 | ||
Intrauterine growth retardation |
Prenatal growth deficiency
Prenatal growth retardation
[ more ] |
0001511 | |
Microcephaly |
Abnormally small skull
Decreased circumference of cranium
Decreased size of skull
Reduced head circumference
Small head circumference
[ more ] |
0000252 | |
Osteolytic defects of the middle phalanx of the 4th toe | 0100453 | ||
Seizure | 0001250 | ||
Spasticity |
Involuntary muscle stiffness, contraction, or spasm
|
0001257 | |
Tachypnea |
Increased respiratory rate or depth of breathing
|
0002789 | |
Tremor | 0001337 | ||
5%-29% of people have these symptoms | |||
Cerebral palsy | 0100021 | ||
Dyspnea |
Trouble breathing
|
0002094 | |
0001332 | |||
Epicanthus |
Eye folds
Prominent eye folds
[ more ] |
0000286 | |
Frontal bossing | 0002007 | ||
High palate |
Elevated palate
Increased palatal height
[ more ] |
0000218 | |
Hypertelorism |
Wide-set eyes
Widely spaced eyes
[ more ] |
0000316 | |
Long philtrum | 0000343 | ||
Multiple lipomas |
Multiple fatty lumps
|
0001012 | |
Narrow face |
Decreased breadth of face
Decreased width of face
[ more ] |
0000275 | |
Pectus excavatum |
Funnel chest
|
0000767 | |
Trigonocephaly |
Triangular skull shape
Wedge shaped skull
[ more ] |
0000243 | |
Upslanted palpebral fissure |
Upward slanting of the opening between the eyelids
|
0000582 | |
Ventriculomegaly | 0002119 | ||
Wide nasal bridge |
Broad nasal bridge
Broad nasal root
Broadened nasal bridge
Increased breadth of bridge of nose
Increased breadth of nasal bridge
Increased width of bridge of nose
Increased width of nasal bridge
Nasal bridge broad
Wide bridge of nose
Widened nasal bridge
[ more ] |
0000431 | |
1%-4% of people have these symptoms | |||
Abnormal facial shape |
Unusual facial appearance
|
0001999 | |
Percent of people who have these symptoms is not available through HPO | |||
Agenesis of corpus callosum | 0001274 | ||
Anteverted nares |
Nasal tip, upturned
Upturned nasal tip
Upturned nose
Upturned nostrils
[ more ] |
0000463 | |
Apneic episodes precipitated by illness, fatigue, stress | 0002872 | ||
Basal ganglia cysts | 0006799 | ||
Cerebral atrophy |
Degeneration of cerebrum
|
0002059 | |
Chronic lactic acidosis | 0004925 | ||
Decreased activity of the pyruvate dehydrogenase complex | 0002928 | ||
Episodic ataxia | 0002131 | ||
Flared nostrils | 0000454 | ||
Generalized hypotonia |
Decreased muscle tone
Low muscle tone
[ more ] |
0001290 | |
Hyperalaninemia |
Increased blood alanine
Increased serum alanine
[ more ] |
0003348 | |
Increased CSF lactate | 0002490 | ||
Increased serum lactate | 0002151 | ||
Infantile onset |
Onset in first year of life
Onset in infancy
[ more ] |
0003593 | |
Intellectual disability |
Mental deficiency
Mental retardation
Mental retardation, nonspecific
Mental-retardation
[ more ] |
0001249 | |
Psychomotor retardation | 0025356 | ||
Drooping upper eyelid
|
0000508 | ||
Severe lactic acidosis | 0004900 | ||
Small for gestational age |
Birth weight less than 10th percentile
Cause Pyruvate dehydrogenase complex (PDC) deficiency is caused by having low levels of one or more
When the pyruvate dehydrogenase complex is not working properly, pyruvate can’t be converted to acetyl-CoA. This causes pyruvate to build up in cells. The pyruvate instead is turned into lactic acid, which is toxic to the body in large amounts and causes lactic acidosis. When pyruvate isn’t converted into acetyl-CoA, the body also can’t go through the citric acid cycle. Therefore, enough energy is not made for the body to function properly. The brain is a part of the body that requires a lot of energy, so the symptoms that are first seen when energy is lacking often affect the brain. The signs and symptoms of PDC deficiency are variable because the amount of enzyme that is available to create energy varies in different people with the disease.[1] PDC deficiency is caused by genetic changes ( Diagnosis Pyruvate dehydrogenase complex (PDC) deficiency is suspected in people who have lactic acidosis or signs of early-onset neurological disease such as
A diagnosis of PDC deficiency can be confirmed by testing the activity of the pyruvate dehydrogenase complex and the activity of all of the specific Testing Resources
Treatment The goal of the treatment for pyruvate dehydrogenase complex (PDC) deficiency is to stimulate the pyruvate dehydrogenase complex to produce as much energy as possible. This can prevent immediate worsening of the disease.[1][4] Treatment options typically include supplementing cofactors including carnitine, thiamine, and lipoic acid. These are substances in the body that help the chemical reactions in the
A medication called dichloroacetate may help treat some people with PDC deficiency. Doctors may also recommend a diet that is high in fats and low in carbohydrates (ketogenic diet). This can help prevent lactic acidosis but typically does not stop neurological symptoms.[1] Medications to help prevent Related diseasesRelated 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.
OrganizationsSupport 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 moreThese 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
In-Depth Information
References
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