Overview
Combined malonic and methylmalonic acidemia (CMAMMA) is a rare inherited metabolic disorder in which the body cannot properly break down certain fats and proteins. This leads to a buildup of two specific acids — malonic acid and methylmalonic acid — in the blood and urine. The condition is caused by mutations in the ACSF3 gene, which provides instructions for making an enzyme needed in an important energy-producing pathway inside cells called the mitochondria. Symptoms of CMAMMA can vary widely, even among people in the same family. Some individuals are diagnosed in infancy or early childhood with feeding difficulties, failure to thrive, low blood sugar, seizures, and developmental delays. Others may not show symptoms until later in childhood or even adulthood, when they may experience fatigue, memory and concentration problems, psychiatric symptoms like depression or anxiety, and neurological issues such as movement difficulties. During times of illness or fasting, symptoms can worsen significantly, sometimes leading to a metabolic crisis. CMAmMA has historically been underdiagnosed because standard newborn screening for methylmalonic acidemia may not always detect it. Treatment is mainly supportive and focuses on preventing metabolic crises through dietary management, avoiding prolonged fasting, and sometimes supplementing with specific vitamins or nutrients. There is currently no cure, but early diagnosis and careful management can help improve quality of life and reduce the risk of serious complications.
Also known as:
Key symptoms:
Fatigue and low energyFailure to thrive in infancyFeeding difficultiesLow blood sugar (hypoglycemia)SeizuresDevelopmental delaysMemory and concentration problemsDepression or anxietyMovement difficulties or clumsinessMuscle weaknessEpisodes of metabolic crisis during illnessLearning difficultiesSpeech delaysNausea and vomitingIrritability
Clinical phenotype terms (26)— hover any for plain English
Autosomal recessive
Passed on when both parents carry the same gene change; often skips generations
Variable
Can begin at different ages, from infancy through adulthood
Treatments
No FDA-approved treatments are currently listed for Combined malonic and methylmalonic acidemia.
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Specialists
View all specialists →No specialists are currently listed for Combined malonic and methylmalonic acidemia.
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 Combined malonic and methylmalonic acidemia.
Community
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Caregiver Resources
NORD Caregiver Resources
Support, advocacy, and financial assistance for caregivers of rare disease patients.
Mental Health Support
Rare disease caregiving can be isolating. Connect with counseling and peer support.
Family & Caregiver Grants
Financial assistance programs specifically for caregivers of rare disease patients.
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.How severe is my (or my child's) form of CMAMMA, and what symptoms should I watch for?,What dietary plan should we follow, and do we need to see a metabolic dietitian?,What should we do during illness to prevent a metabolic crisis?,Should we carry an emergency letter, and what should it say?,Are there any supplements like carnitine that might help?,How often should we have follow-up appointments and lab tests?,Are there any clinical trials or new treatments being studied for CMAMMA?
Common questions about Combined malonic and methylmalonic acidemia
What is Combined malonic and methylmalonic acidemia?
Combined malonic and methylmalonic acidemia (CMAMMA) is a rare inherited metabolic disorder in which the body cannot properly break down certain fats and proteins. This leads to a buildup of two specific acids — malonic acid and methylmalonic acid — in the blood and urine. The condition is caused by mutations in the ACSF3 gene, which provides instructions for making an enzyme needed in an important energy-producing pathway inside cells called the mitochondria. Symptoms of CMAMMA can vary widely, even among people in the same family. Some individuals are diagnosed in infancy or early childhood
How is Combined malonic and methylmalonic acidemia inherited?
Combined malonic and methylmalonic acidemia follows a autosomal recessive inheritance pattern. Genetic counseling can help families understand recurrence risk and testing options.