Lipoic acid synthetase deficiency

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ORPHA:401859OMIM:614462E88.8
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Overview

Lipoic acid synthetase deficiency (also called LIAS deficiency) is an extremely rare inherited metabolic disorder caused by problems in the gene that makes lipoic acid synthetase, an enzyme the body needs to produce lipoic acid. Lipoic acid is a critical helper molecule (cofactor) that several important enzymes in the body depend on to break down sugars and amino acids for energy. When lipoic acid cannot be made properly, these energy-producing pathways in the cells fail, leading to a buildup of harmful substances and a shortage of cellular energy. Babies with this condition typically become sick very early in life, often in the newborn period. Common problems include a dangerous buildup of lactic acid in the blood (lactic acidosis), seizures that are difficult to control, poor muscle tone, feeding difficulties, and failure to grow and develop normally. The brain is particularly affected, and many children show abnormalities on brain imaging. Other organs such as the heart and liver may also be involved. There is currently no cure for lipoic acid synthetase deficiency. Treatment is mainly supportive and focuses on managing seizures, correcting metabolic imbalances, providing nutritional support, and addressing complications as they arise. Some patients have been tried on supplemental lipoic acid or other cofactors, but results have been limited. Because this disease affects fundamental energy production in cells, the outlook is unfortunately serious, and many affected children experience significant developmental challenges and shortened lifespan.

Key symptoms:

Severe lactic acidosis (dangerous acid buildup in the blood)Seizures that are hard to controlPoor muscle tone (floppiness)Feeding difficultiesFailure to thrive and poor weight gainDevelopmental delay or intellectual disabilityAbnormal brain development seen on MRIEpisodes of metabolic crisisBreathing difficultiesLiver problemsHeart problems (cardiomyopathy)Low energy and excessive sleepinessMovement abnormalitiesElevated glycine levels in the blood

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 Lipoic acid synthetase deficiency.

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No actively recruiting trials found for Lipoic acid synthetase deficiency at this time.

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No specialists are currently listed for Lipoic acid synthetase deficiency.

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

No travel grants are currently matched to Lipoic acid synthetase deficiency.

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Community

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Latest news about Lipoic acid synthetase deficiency

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Caregiver Resources

NORD Caregiver Resources

Support, advocacy, and financial assistance for caregivers of rare disease patients.

Mental Health Support

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Family & Caregiver Grants

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Social Security Disability

Learn how rare disease patients may qualify for SSDI/SSI benefits.

Questions for your doctor

Bring these to your next appointment

  • Q1.What specific genetic variants were found in my child's LIAS gene, and what do they mean for the severity of the disease?,Are there any experimental treatments or clinical trials that might be appropriate for my child?,What is the emergency plan if my child has a metabolic crisis, and what should I tell emergency room doctors?,Would supplementation with lipoic acid or other vitamins be worth trying in my child's case?,How often should my child have brain imaging, heart checks, and metabolic blood tests?,What developmental and therapy services should we set up, and how can we access them?,Should other family members be tested as carriers, and what are the options for future pregnancies?

Common questions about Lipoic acid synthetase deficiency

What is Lipoic acid synthetase deficiency?

Lipoic acid synthetase deficiency (also called LIAS deficiency) is an extremely rare inherited metabolic disorder caused by problems in the gene that makes lipoic acid synthetase, an enzyme the body needs to produce lipoic acid. Lipoic acid is a critical helper molecule (cofactor) that several important enzymes in the body depend on to break down sugars and amino acids for energy. When lipoic acid cannot be made properly, these energy-producing pathways in the cells fail, leading to a buildup of harmful substances and a shortage of cellular energy. Babies with this condition typically become

How is Lipoic acid synthetase deficiency inherited?

Lipoic acid synthetase deficiency follows a autosomal recessive inheritance pattern. Genetic counseling can help families understand recurrence risk and testing options.

At what age does Lipoic acid synthetase deficiency typically begin?

Typical onset of Lipoic acid synthetase deficiency is neonatal. Age of onset can vary across affected individuals.