Overview
Ethylmalonic encephalopathy (EE) is a very rare and serious inherited metabolic disorder that affects the brain, blood vessels, and digestive system. It is caused by a faulty gene called ETHE1, which leads to a buildup of toxic substances — especially hydrogen sulfide and ethylmalonic acid — in the body. These substances damage the brain, small blood vessels, and muscles over time. The disease is also sometimes referred to as ETHE1 deficiency. Babies with ethylmalonic encephalopathy usually appear normal at birth but begin showing symptoms in the first few months of life. The most common signs include delayed development, weak muscle tone (called hypotonia), seizures, and small purple or red spots on the skin caused by bleeding under the surface (called petechiae). Children may also have chronic diarrhea and episodes where their hands and feet turn bluish-purple due to poor blood flow (acrocyanosis). There is currently no cure for ethylmalonic encephalopathy. Treatment focuses on managing symptoms and slowing the buildup of toxic substances. Some children have been treated with a combination of N-acetylcysteine and metronidazole, which can reduce hydrogen sulfide levels and may help stabilize the condition. The disease is progressive and life-threatening, and most affected children experience significant neurological decline. Early diagnosis and specialist care are essential to give children the best possible quality of life.
Key symptoms:
Delayed development and loss of previously gained skillsWeak muscle tone (hypotonia)SeizuresSmall red or purple spots on the skin (petechiae) caused by tiny bleedsBluish-purple discoloration of hands and feet (acrocyanosis)Chronic or recurring diarrheaIntellectual disabilityDifficulty walking or loss of ability to walkAbnormal eye movementsSpasticity (stiff or tight muscles)Feeding difficultiesEpisodes of metabolic crisis with worsening neurological symptomsBrain abnormalities visible on MRI scans
Clinical phenotype terms (18)— hover any for plain English
Autosomal recessive
Passed on when both parents carry the same gene change; often skips generations
Infantile
Begins in infancy, roughly 1 month to 2 years old
Treatments
No FDA-approved treatments are currently listed for Ethylmalonic encephalopathy.
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Specialists
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Treatment Centers
8 centersBaylor College of Medicine Rare Disease Center ↗
Baylor College of Medicine
📍 Houston, TX
🏥 NORDStanford Medicine Rare Disease Center ↗
Stanford Medicine
📍 Stanford, CA
🔬 UDNNIH Clinical Center Undiagnosed Diseases Program ↗
National Institutes of Health
📍 Bethesda, MD
🔬 UDNUCLA UDN Clinical Site ↗
UCLA Health
📍 Los Angeles, CA
🔬 UDNBaylor College of Medicine UDN Clinical Site ↗
Baylor College of Medicine
📍 Houston, TX
🔬 UDNHarvard/MGH UDN Clinical Site ↗
Massachusetts General Hospital
📍 Boston, MA
🏥 NORDMayo Clinic Center for Individualized Medicine ↗
Mayo Clinic
📍 Rochester, MN
👤 Mayo Clinic Center for Individualized Medicine
🏥 NORDUCLA Rare Disease Day Program ↗
UCLA Health
📍 Los Angeles, CA
Travel Grants
No travel grants are currently matched to Ethylmalonic encephalopathy.
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Caregiver Resources
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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 is the best treatment plan for my child right now, and how will we know if it is working?,Should my child start N-acetylcysteine and metronidazole, and what side effects should I watch for?,What does my child's brain MRI show, and what does it mean for their future development?,Are there any clinical trials or research studies that my child might be eligible for?,What signs should prompt me to take my child to the emergency room immediately?,What therapies — such as physiotherapy, speech therapy, or occupational therapy — should my child be receiving?,Should other family members be tested, and what are the chances of this happening in a future pregnancy?
Common questions about Ethylmalonic encephalopathy
What is Ethylmalonic encephalopathy?
Ethylmalonic encephalopathy (EE) is a very rare and serious inherited metabolic disorder that affects the brain, blood vessels, and digestive system. It is caused by a faulty gene called ETHE1, which leads to a buildup of toxic substances — especially hydrogen sulfide and ethylmalonic acid — in the body. These substances damage the brain, small blood vessels, and muscles over time. The disease is also sometimes referred to as ETHE1 deficiency. Babies with ethylmalonic encephalopathy usually appear normal at birth but begin showing symptoms in the first few months of life. The most common sign
How is Ethylmalonic encephalopathy inherited?
Ethylmalonic encephalopathy follows a autosomal recessive inheritance pattern. Genetic counseling can help families understand recurrence risk and testing options.
At what age does Ethylmalonic encephalopathy typically begin?
Typical onset of Ethylmalonic encephalopathy is infantile. Age of onset can vary across affected individuals.