Multiple mitochondrial dysfunctions syndrome type 4

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ORPHA:457406OMIM:616370E88.8
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Overview

Multiple mitochondrial dysfunctions syndrome type 4 (MMDS4) is an extremely rare genetic disorder that affects the mitochondria — the tiny power plants inside every cell that produce energy. In this condition, several important enzymes within the mitochondria do not work properly because of problems with iron-sulfur cluster assembly. Iron-sulfur clusters are small chemical structures that many enzymes need in order to function. When these clusters cannot be built correctly, multiple energy-producing pathways in the cell break down at the same time. MMDS4 is caused by mutations in the BOLA3 gene. Babies with this condition typically become sick very early in life, often in the newborn period or during infancy. Common symptoms include severe lactic acidosis (a dangerous buildup of acid in the blood), breathing difficulties, poor feeding, weak muscle tone, seizures, and failure to grow and develop normally. Brain abnormalities may also be seen on imaging. The disease can affect the heart, brain, and other organs because they all depend heavily on mitochondrial energy. Unfortunately, there is currently no cure for MMDS4. Treatment is supportive and focuses on managing symptoms such as seizures, metabolic crises, and nutritional needs. The prognosis is generally very poor, with many affected children experiencing severe disability or early death. Research into mitochondrial diseases is ongoing, and families are encouraged to connect with metabolic specialists and genetic counselors for the most up-to-date guidance.

Also known as:

Key symptoms:

Severe buildup of lactic acid in the bloodPoor muscle tone (floppiness)SeizuresDifficulty breathing or respiratory failurePoor feeding and failure to thriveDevelopmental delay or regressionBrain abnormalities seen on MRIHeart problems (cardiomyopathy)Lethargy or extreme tirednessEpisodes of metabolic crisisAbnormal movementsLiver dysfunctionVision problemsIntellectual disability

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 Multiple mitochondrial dysfunctions syndrome type 4.

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No actively recruiting trials found for Multiple mitochondrial dysfunctions syndrome type 4 at this time.

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No specialists are currently listed for Multiple mitochondrial dysfunctions syndrome type 4.

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 Multiple mitochondrial dysfunctions syndrome type 4.

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Community

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Latest news about Multiple mitochondrial dysfunctions syndrome type 4

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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.What specific BOLA3 mutations does my child have, and what does that mean for their outlook?,What symptoms should I watch for that would require emergency care?,Are there any supplements or vitamins that might help, even a little?,What feeding and nutritional support does my child need?,Should we involve palliative care, and what does that look like for our family?,Is genetic counseling available for our family to understand the risk for future pregnancies?,Are there any clinical trials or research studies we could participate in?

Common questions about Multiple mitochondrial dysfunctions syndrome type 4

What is Multiple mitochondrial dysfunctions syndrome type 4?

Multiple mitochondrial dysfunctions syndrome type 4 (MMDS4) is an extremely rare genetic disorder that affects the mitochondria — the tiny power plants inside every cell that produce energy. In this condition, several important enzymes within the mitochondria do not work properly because of problems with iron-sulfur cluster assembly. Iron-sulfur clusters are small chemical structures that many enzymes need in order to function. When these clusters cannot be built correctly, multiple energy-producing pathways in the cell break down at the same time. MMDS4 is caused by mutations in the BOLA3 ge

How is Multiple mitochondrial dysfunctions syndrome type 4 inherited?

Multiple mitochondrial dysfunctions syndrome type 4 follows a autosomal recessive inheritance pattern. Genetic counseling can help families understand recurrence risk and testing options.

At what age does Multiple mitochondrial dysfunctions syndrome type 4 typically begin?

Typical onset of Multiple mitochondrial dysfunctions syndrome type 4 is neonatal. Age of onset can vary across affected individuals.