Pyruvate carboxylase deficiency, severe neonatal type

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ORPHA:353314OMIM:266150E74.4
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Overview

Pyruvate carboxylase deficiency, severe neonatal type (also called Type B or French type) is a very rare and serious inherited metabolic disorder that affects how the body produces energy and builds important molecules. Pyruvate carboxylase is an enzyme found in the mitochondria (the energy factories inside cells) that plays a critical role in making glucose (blood sugar), producing energy for the brain, and building fats needed for brain development. When this enzyme is missing or severely reduced, toxic substances build up in the blood and the body cannot produce enough energy to support vital organs, especially the brain and liver. In the severe neonatal form, symptoms appear within the first few days to weeks of life. Babies typically show severe lactic acidosis (too much acid in the blood), low blood sugar, high ammonia levels, seizures, poor feeding, extreme lethargy, and failure to thrive. The liver may become enlarged, and there is often profound developmental delay. Brain abnormalities, including loss of brain tissue and abnormal brain structure, are common. Unfortunately, the severe neonatal type carries a very poor prognosis. There is currently no cure, and treatment is mainly supportive. Efforts focus on correcting metabolic imbalances, managing seizures, and providing nutritional support. Despite these measures, most affected infants do not survive beyond the first few months of life. Research into potential therapies, including gene therapy and enzyme replacement, is ongoing but remains in early stages.

Also known as:

Key symptoms:

Severe buildup of acid in the blood (lactic acidosis)Very low blood sugar (hypoglycemia)High ammonia levels in the bloodSeizures starting in the first days of lifeExtreme sleepiness or unresponsivenessPoor feeding and difficulty suckingFailure to gain weight and growEnlarged liverAbnormal muscle tone (floppy or stiff)Severe intellectual disabilityBreathing difficultiesAbnormal brain developmentEpisodes of metabolic crisisVomiting

Inheritance

Autosomal recessive

Passed on when both parents carry the same gene change; often skips generations

Age of Onset

Neonatal

Begins at or shortly after birth (first 4 weeks)

Orphanet ↗OMIM ↗NORD ↗

Treatments

No FDA-approved treatments are currently listed for Pyruvate carboxylase deficiency, severe neonatal type.

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No specialists are currently listed for Pyruvate carboxylase deficiency, severe neonatal type.

View NORD Rare Disease Centers ↗Undiagnosed Disease Network ↗

Treatment Centers

8 centers
🏥 NORD

Baylor College of Medicine Rare Disease Center

Baylor College of Medicine

📍 Houston, TX

🏥 NORD

Stanford Medicine Rare Disease Center

Stanford Medicine

📍 Stanford, CA

🔬 UDN

NIH Clinical Center Undiagnosed Diseases Program

National Institutes of Health

📍 Bethesda, MD

🔬 UDN

UCLA UDN Clinical Site

UCLA Health

📍 Los Angeles, CA

🔬 UDN

Baylor College of Medicine UDN Clinical Site

Baylor College of Medicine

📍 Houston, TX

🔬 UDN

Harvard/MGH UDN Clinical Site

Massachusetts General Hospital

📍 Boston, MA

🏥 NORD

Mayo Clinic Center for Individualized Medicine

Mayo Clinic

📍 Rochester, MN

👤 Mayo Clinic Center for Individualized Medicine

🏥 NORD

UCLA Rare Disease Day Program

UCLA Health

📍 Los Angeles, CA

Travel Grants

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Community

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Caregiver Resources

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Social Security Disability

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Questions for your doctor

Bring these to your next appointment

  • Q1.What is the expected course of this disease for my baby?,Are there any treatments or supplements that might help, even partially?,Should we involve a palliative care team, and what does that look like?,What are the chances of this happening again in a future pregnancy, and what testing is available?,Are there any clinical trials or experimental treatments we should know about?,What emergency signs should we watch for at home, and what should we do if they occur?,Can you connect us with a genetic counselor and family support services?

Common questions about Pyruvate carboxylase deficiency, severe neonatal type

What is Pyruvate carboxylase deficiency, severe neonatal type?

Pyruvate carboxylase deficiency, severe neonatal type (also called Type B or French type) is a very rare and serious inherited metabolic disorder that affects how the body produces energy and builds important molecules. Pyruvate carboxylase is an enzyme found in the mitochondria (the energy factories inside cells) that plays a critical role in making glucose (blood sugar), producing energy for the brain, and building fats needed for brain development. When this enzyme is missing or severely reduced, toxic substances build up in the blood and the body cannot produce enough energy to support vit

How is Pyruvate carboxylase deficiency, severe neonatal type inherited?

Pyruvate carboxylase deficiency, severe neonatal type follows a autosomal recessive inheritance pattern. Genetic counseling can help families understand recurrence risk and testing options.

At what age does Pyruvate carboxylase deficiency, severe neonatal type typically begin?

Typical onset of Pyruvate carboxylase deficiency, severe neonatal type is neonatal. Age of onset can vary across affected individuals.