Pyruvate carboxylase deficiency

Title

Other Names:

PC deficiency; Ataxia with lactic acidosis 2; Leigh necrotizing encephalopathy due to pyruvate carboxylase deficiency; PC deficiency; Ataxia with lactic acidosis 2; Leigh necrotizing encephalopathy due to pyruvate carboxylase deficiency; Leigh syndrome due to pyruvate carboxylase deficiency See More

Categories:

Metabolic disorders

Summary Summary

Pyruvate carboxylase deficiency is an inherited disorder that causes lactic acid and other potentially toxic compounds to accumulate in the blood. High levels of these substances can damage the body's organs and tissues, particularly in the nervous system. Researchers have identified at least three types of pyruvate carboxylase deficiency, types A, B, and C, which are distinguished by the severity of their signs and symptoms. This condition is caused by mutations in the PC gene and inherited in an autosomal recessive pattern.^[1]

Last updated: 6/1/2015

Symptoms 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.

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Medical Terms	Other Names	Learn More: HPO ID
Percent of people who have these symptoms is not available through HPO
Autosomal recessive inheritance		0000007
Clonus		0002169
Congenital onset	Symptoms present at birth	0003577
Generalized hypotonia	Decreased muscle tone Low muscle tone [ more ]	0001290
Global developmental delay		0001263
Hepatomegaly	Enlarged liver	0002240
Hyperalaninemia	Increased blood alanine Increased serum alanine [ more ]	0003348
Hypoglycemia	Low blood sugar	0001943
Increased serum lactate		0002151
Increased serum pyruvate		0003542
Intellectual disability	Mental deficiency Mental retardation Mental retardation, nonspecific Mental-retardation [ more ]	0001249
Lactic acidosis	Increased lactate in body	0003128
Leukodystrophy		0002415
Muscular hypotonia	Low or weak muscle tone	0001252
Neuronal loss in the cerebral cortex		0007190
Periventricular leukomalacia		0006970
Proximal renal tubular acidosis		0002049
Psychomotor retardation		0025356
Seizures	Seizure	0001250

Showing of 19 |

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Last updated: 3/1/2020

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Inheritance Inheritance

Pyruvate carboxylase deficiency is inherited in an autosomal recessive manner.^[2] This means that both copies of the disease-causing gene in each cell (usually one inherited from each parent) must have a mutation for an individual to be affected. Individuals who carry one mutated copy of the gene are referred to as carriers. Carriers typically do not have any signs or symptoms of the condition. When two carriers for an autosomal recessive condition have children, each child has a 25% (1 in 4) risk to have the condition, a 50% (1 in 2) risk to be an unaffected carrier like each of the parents, and a 25% risk to not have the condition and not be a carrier (i.e. to inherit both normal genes). In other words, each child born to two carriers has a 75% (3 in 4) chance to be unaffected.

De novo mutations (new mutations that occur for the first time in an individual and are not inherited from a parent) have been reported for this condition.^[3] This means that in some cases, an affected individual may have only one parent who is a carrier for the condition.

Carrier testing for at-risk relatives and prenatal testing for pregnancies at increased risk may be possible through laboratories offering custom mutation analysis if the disease-causing mutations in a family are known.^[3] Individuals interested in learning more about genetic risks to themselves or family members, or about genetic testing for this condition, should speak with a genetics professional.

Last updated: 3/20/2013

Diagnosis 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.

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.

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.
You can submit a question to Ask the Mito Doc, a service of the United Mitochondrial Diseases Foundation. Information contained in Ask the Mito Doc^SM is for informational and educational purposes only.

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
Several inborn errors of metabolism have certain features similar to those of PC deficiency. Similar disorders to consider in the differential diagnosis include biotinidase deficiency, holocarboxylase synthase deficiency, pyruvate dehydrogenase deficiency, as well as respiratory chain disorders, tricarboxylic acid cycle disorder, and gluconeogenic defects. Visit the Orphanet disease page for more information.

Conditions with similar signs and symptoms from Orphanet

Several inborn errors of metabolism have certain features similar to those of PC deficiency. Similar disorders to consider in the differential diagnosis include biotinidase deficiency, holocarboxylase synthase deficiency, pyruvate dehydrogenase deficiency, as well as respiratory chain disorders, tricarboxylic acid cycle disorder, and gluconeogenic defects.

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

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
United Mitochondrial Disease Foundation
8085 Saltsburg Road, Suite 201
Pittsburgh, PA 15239
Toll-free: 1-888-317-8633
Telephone: +1-412-793-8077
Fax: +1-412-793-6477
E-mail: info@umdf.org
Website: https://www.umdf.org

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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 Pyruvate carboxylase deficiency. 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.

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.
Medscape Reference provides information on this topic. You may need to register to view the medical textbook, but registration is free.
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.
The Neuromuscular Disease Center at Washington University provides information about Leigh syndrome.
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 Pyruvate carboxylase deficiency. Click on the link to view a sample search on this topic.

Selected Full-Text Journal Articles

Huntsman RJ, Sinclair DB, Bhargava R, Chan A. Atypical presentations of Leigh syndrome: A case series and review. Pediatr Neurol 2005;32:334-340.

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

Is there any chance of having a healthy baby for parents who have the condition or are carriers? See answer

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References References

Pyruvate carboxylase deficiency. Genetics Home Reference. August 2006; http://ghr.nlm.nih.gov/condition/pyruvate-carboxylase-deficiency. Accessed 6/1/2015.
Pyruvate carboxylase deficiency. Genetics Home Reference. August 2006; http://ghr.nlm.nih.gov/condition/pyruvate-carboxylase-deficiency. Accessed 3/20/2013.
Dong Wang and Darryl De Vivo. Pyruvate Carboxylase Deficiency. GeneReviews. July 21, 2011; http://www.ncbi.nlm.nih.gov/books/NBK6852/. Accessed 3/20/2013.

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