Glutamate-cysteine ligase deficiency

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ORPHA:33574OMIM:230450D55.1
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Overview

Glutamate-cysteine ligase (GCL) deficiency is a very rare inherited condition that affects the body's ability to make an important antioxidant called glutathione. Glutathione acts like a shield inside your cells, protecting them from damage caused by harmful molecules called free radicals. When the enzyme glutamate-cysteine ligase does not work properly, the body cannot produce enough glutathione, and cells — especially red blood cells — become vulnerable to damage and early destruction. This condition is also sometimes called GCL deficiency or gamma-glutamylcysteine synthetase deficiency. The most common effect of this disease is a type of anemia called hemolytic anemia, where red blood cells break down faster than the body can replace them. This leads to symptoms like fatigue, pale skin, yellowing of the skin or eyes (jaundice), and an enlarged spleen. In some people, the disease also affects the nervous system, causing problems with movement, coordination, and thinking. Symptoms can range from mild to more serious depending on the person. Treatment is mainly focused on managing symptoms. There is no cure at this time. Doctors may recommend folic acid supplements, blood transfusions during severe episodes, and avoiding things that can trigger red blood cell breakdown, such as certain medications or infections. With careful management, many people can live relatively stable lives, though ongoing medical monitoring is important.

Also known as:

Key symptoms:

Chronic fatigue and low energyPale skin or pallorYellowing of the skin or whites of the eyes (jaundice)Enlarged spleen (splenomegaly)Anemia (low red blood cell count)Episodes of sudden red blood cell breakdown (hemolytic crises)Dark or tea-colored urine during hemolytic episodesRapid or irregular heartbeatShortness of breathProblems with balance and coordination (ataxia)Muscle weakness or stiffnessCognitive difficulties or intellectual disability (in some cases)Peripheral neuropathy (tingling or weakness in hands and feet)

Clinical phenotype terms (15)— hover any for plain English
Spinocerebellar tract degenerationHP:0002503DyslexiaHP:0010522
Inheritance

Autosomal recessive

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

Age of Onset

Variable

Can begin at different ages, from infancy through adulthood

Orphanet ↗OMIM ↗NORD ↗

Treatments

No FDA-approved treatments are currently listed for Glutamate-cysteine ligase deficiency.

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No actively recruiting trials found for Glutamate-cysteine ligase deficiency at this time.

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No specialists are currently listed for Glutamate-cysteine ligase 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 Glutamate-cysteine ligase deficiency.

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Community

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Caregiver Resources

NORD Caregiver Resources

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Mental Health Support

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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.Which gene is causing the problem in my case — GCLC or GCLM — and what does that mean for my symptoms?,What medications, supplements, or foods should I strictly avoid to prevent a hemolytic crisis?,How often should I have blood tests to monitor my red blood cell levels and overall health?,Is there any risk of neurological complications in my case, and how would we monitor for them?,Are there any clinical trials or emerging treatments I should know about?,Should my family members be tested for this condition?,What should I do — and who should I call — if I think I am having a hemolytic crisis?

Common questions about Glutamate-cysteine ligase deficiency

What is Glutamate-cysteine ligase deficiency?

Glutamate-cysteine ligase (GCL) deficiency is a very rare inherited condition that affects the body's ability to make an important antioxidant called glutathione. Glutathione acts like a shield inside your cells, protecting them from damage caused by harmful molecules called free radicals. When the enzyme glutamate-cysteine ligase does not work properly, the body cannot produce enough glutathione, and cells — especially red blood cells — become vulnerable to damage and early destruction. This condition is also sometimes called GCL deficiency or gamma-glutamylcysteine synthetase deficiency. Th

How is Glutamate-cysteine ligase deficiency inherited?

Glutamate-cysteine ligase deficiency follows a autosomal recessive inheritance pattern. Genetic counseling can help families understand recurrence risk and testing options.