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

The Human Phenotype Ontology (HPO) provides the following list of features that have been reported in people with this condition. Much of the information in the HPO comes from Orphanet, a European rare disease database. If available, the list includes a rough estimate of how common a feature is (its frequency). Frequencies are based on a specific study and may not be representative of all studies. You can use the MedlinePlus Medical Dictionary for definitions of the terms below.

Signs and Symptoms	Approximate number of patients (when available)
Autosomal recessive inheritance	-
Clonus	-
Congenital onset	-
Hepatomegaly	-
Hyperalaninemia	-
Hypoglycemia	-
Increased serum lactate	-
Increased serum pyruvate	-
Intellectual disability	-
Lactic acidosis	-
Muscular hypotonia	-
Neuronal loss in the cerebral cortex	-
Periventricular leukomalacia	-
Proximal renal tubular acidosis	-
Seizures	-

Last updated: 9/1/2017

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.

Treatment 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

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.

Do you have updated information on this condition? Let us know.

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

Children Living with Inherited Metabolic Diseases (CLIMB)
Climb Building
176 Nantwich Road
Crewe CW2 6BG
United Kingdom
Toll-free: 0800 652 3181
Telephone: 0845 241 2173
E-mail: contact@climb.org.uk
Website: http://www.climb.org.uk
United Mitochondrial Disease Foundation
8085 Saltsburg Road, Suite 201
Pittsburgh, PA 15239
Toll-free: 888-317-8633
Telephone: 412-793-8077
Fax: 412-793-6477
E-mail: info@umdf.org
Website: http://www.umdf.org

Do you know of an organization? Send us your suggestions.

Living With Living With

Living with a genetic or rare disease can impact the daily lives of patients and families. These resources can help families navigate various aspects of living with a rare disease.

Healthcare Resources

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

Genetics 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 GeneTests, 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.

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

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.

News & Events News & Events

News

Don’t Miss the NCATS Toolkit for Patient-Focused Therapy Development Event
August 31, 2017
Funding Opportunities Now Available for the Undiagnosed Diseases Network (UDN) Phase II
August 30, 2017
IRDiRC Goals 2017-2027: New Rare Disease Research Goals for the Next Decade
August 10, 2017

NCATS Co-Sponsored Conferences

Nutritional Interventions in Primary Mitochondrial Disorders: Developing an Evidence Base Tuesday, December 2, 2014 - Wednesday, December 3, 2014
Location: NIH Campus, Bethesda, MD
Description: The goal of this meeting is to explore the use of nutritional interventions, including dietary supplements, in primary mitochondrial disorders (PMD); identify gaps in knowledge; develop a research agenda; and identify research opportunities to promote an evidence base for the use of nutritional interventions in primary mitochondrial disorders.

Contact: Kathryn Camp, MS, RD, CSP,(301) 435-3608, campkm@od.nih.gov

Co-funding Institute(s): Office of Dietary Supplements, Office of Rare Diseases Research
2013 Neurobiology of Disease in Children Symposium: Mitochondrial Disease Wednesday, October 30, 2013 - Wednesday, October 30, 2013
Location: Austin, TX
Description: The topic for the 2013 NDC Symposium is Mitochondrial Disease. The NDC Symposium is a forum for preeminent investigators assembled to discuss recent accomplishments and future directions with a large group of child neurologists, program officers from the National Institutes of Health, and members of dedicated foundations and associations.

Contact:

Co-funding Institute(s): National Institute of Neurological Disorders and Stroke, Office of Rare Diseases Research
- Agenda ( - 38KB)

GARD Answers GARD Answers

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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.

Do you know of a review article? Send us your suggestions.