Methylmalonic acidemia with homocystinuria, type cblX

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ORPHA:369962OMIM:309541E71.1
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Overview

Methylmalonic acidemia with homocystinuria, type cblX (also called cobalamin X deficiency or cblX type) is an extremely rare inherited metabolic disorder that affects how the body processes vitamin B12 (cobalamin). It is caused by mutations in the HCFC1 gene, which plays a role in regulating the enzymes needed to properly use vitamin B12 in the body. When these enzymes do not work correctly, harmful substances like methylmalonic acid and homocysteine build up in the blood and urine, while the body cannot make enough of certain essential molecules. This condition typically presents in early infancy or the newborn period. Affected babies may show poor feeding, failure to thrive, low muscle tone (floppiness), developmental delays, and seizures. Many children develop intellectual disability and may have problems with their eyes, heart, or blood cells. The buildup of toxic substances can damage the brain and other organs over time. Treatment focuses on managing symptoms and reducing the buildup of harmful substances. This may include injections of a special form of vitamin B12 (hydroxocobalamin), a protein-restricted diet, betaine supplements to lower homocysteine levels, and carnitine supplementation. Despite treatment, many affected individuals continue to have significant developmental challenges. Early diagnosis and aggressive management are important to give children the best possible outcomes, though the condition remains difficult to treat and there is currently no cure.

Also known as:

Key symptoms:

Intellectual disabilityDevelopmental delaySeizuresPoor feeding in infancyFailure to thriveLow muscle tone (floppiness)Small head size (microcephaly)Abnormal movementsVision problemsHeart defectsLow blood cell countsElevated methylmalonic acid in blood and urineElevated homocysteine in bloodLethargy or excessive sleepinessBreathing difficulties

Inheritance

X-linked recessive

Carried on the X chromosome; typically affects males more than females

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 Methylmalonic acidemia with homocystinuria, type cblX.

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No actively recruiting trials found for Methylmalonic acidemia with homocystinuria, type cblX at this time.

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No specialists are currently listed for Methylmalonic acidemia with homocystinuria, type cblX.

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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 Methylmalonic acidemia with homocystinuria, type cblX.

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Community

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Caregiver Resources

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Questions for your doctor

Bring these to your next appointment

  • Q1.What is the best treatment plan for my child's specific situation?,How often will my child need hydroxocobalamin injections, and can they be given at home?,What should I do if my child becomes sick — what is the emergency protocol?,What developmental therapies should my child receive, and how often?,Are there any clinical trials or new treatments being studied for this condition?,How will this condition affect my child's learning and development over time?,Should other family members be tested, and what does this mean for future pregnancies?

Common questions about Methylmalonic acidemia with homocystinuria, type cblX

What is Methylmalonic acidemia with homocystinuria, type cblX?

Methylmalonic acidemia with homocystinuria, type cblX (also called cobalamin X deficiency or cblX type) is an extremely rare inherited metabolic disorder that affects how the body processes vitamin B12 (cobalamin). It is caused by mutations in the HCFC1 gene, which plays a role in regulating the enzymes needed to properly use vitamin B12 in the body. When these enzymes do not work correctly, harmful substances like methylmalonic acid and homocysteine build up in the blood and urine, while the body cannot make enough of certain essential molecules. This condition typically presents in early in

How is Methylmalonic acidemia with homocystinuria, type cblX inherited?

Methylmalonic acidemia with homocystinuria, type cblX follows a x-linked recessive inheritance pattern. Genetic counseling can help families understand recurrence risk and testing options.

At what age does Methylmalonic acidemia with homocystinuria, type cblX typically begin?

Typical onset of Methylmalonic acidemia with homocystinuria, type cblX is neonatal. Age of onset can vary across affected individuals.