General Condition Information
Other Names
- Cobalamin C deficiency
- Cobalamin C,D cofactor deficiency
- Disorders of intracellular cobalamin metabolism (cblC, D, E, F, G, J, X)
- Methylmalonic acidemia
- Methylmalonic acidemia (Cbl C, D)
- Methylmalonic acidemia with homocystinuria (Cbl C, D)
- Methylmalonic acidemia with homocystinuria- Cobalamin C, D disorders
- Methylmalonic Acidemia, Cbl C and Cbl D
- Methylmalonic acidemia: cobalamin C, D
Condition Type
Birth Prevalence
- It is estimated that fewer than 70 babies are born with this condition each year in the United States.
- Visit GeneReviews to learn more about how often this condition occurs.
Screening Finding
What is methylmalonic acidemia with homocystinuria
There are different forms of methylmalonic acidemia, each with different causes and treatments. Methylmalonic acidemias are inherited (genetic) conditions that prevent the body from breaking down certain proteins, cholesterol, and fats. Homocystinurias occur when urine releases part of a protein called homocysteine. Methylmalonic acidemia with homocystinuria is a combination of both of these conditions.
Methylmalonic acidemias develop when enzymes that use vitamin B-12 to help digest certain proteins, fats, and cholesterol do not work properly. Homocystinuria results because an enzyme that needs vitamin B-12 cannot turn homocysteine into methionine, an important building block of proteins.
If your baby cannot break down proteins, fats, and cholesterol, toxins can build up. When these toxins are acids, blood can become acidic (acidemia). Also, the buildup of homocysteine can increase the likelihood of blood clots and can cause other damage. Acidemia and increased homocysteine can lead to the signs and symptoms of the condition.
Newborn Screening and Follow-Up
Newborn screening for methylmalonic acidemia with homocystinuria is done using a small amount of blood collected from your baby’s heel. To learn more about this process, visit the Blood Spot Screening page.
During screening, a special machine measures how much of certain substances (called acylcarnitines) are in your baby’s blood. Your body makes these substances when it breaks down food. Babies with high levels of these substances might have methylmalonic acidemia with homocystinuria.
If your baby’s blood spot screening result for methylmalonic acidemia with homocystinuria is out-of-range, your baby’s health care provider will contact you. Together, you will discuss next steps and follow-up plans.
An out-of-range screening result does not mean that your baby definitely has the condition. It does mean that your baby needs more follow-up testing. To learn more about screening results, visit the Blood Spot Screening Results page.
Your baby may need the following tests after an out-of-range screening result:
- Blood and/or urine tests
- Genetic testing using a blood sample
- Small skin sample
You should complete any recommended follow-up testing as soon as possible. Babies with this condition can have serious health problems soon after birth if they are not diagnosed and treated quickly.
False-positive newborn screening results for this condition can happen.
Babies who are given carnitine or who have a lot of bilirubin in their blood may have a false-positive newborn screening result for methylmalonic acidemia with homocystinuria.
Moms with low levels of vitamin B-12 can also have babies with false-positive newborn screening results.
Condition Details
Newborn screening helps babies lead healthier lives. If your baby has an out-of-range result, follow up with your health care provider quickly. It is important to follow their instructions. Your baby may need to get treatment right away, even if they are not showing signs or symptoms. In some cases, your baby’s health care provider may decide it is best to watch (monitor) your baby to decide next steps. Careful monitoring and early treatment will help your baby stay as healthy as possible.
Signs of methylmalonic acidemia with homocystinuria vary. Depending on the condition type, they can appear anytime between the first few days of life up to 14 years of age.
Signs of the condition may include the following:
- Delayed growth and weight gain
- Difficulty feeding
- Small head size
- Skin rash
- Vomiting
- Poor appetite
- Fever
- Sleeping longer or more often
- Floppy arms and legs (hypotonia)
The condition is caused by a change in the MMACHC, MMADHC, LMBRD1, ABCD4, or HCFC1 genes. These genes tell your body how to process vitamin B-12.
Your body needs to process vitamin B-12 to help enzymes that break down proteins, fats, and cholesterol from your diet.
Without these working genes, your baby’s body cannot process vitamin B-12. As a result, your baby cannot properly break down food and remove waste.
Methylmalonic acidemia with homocystinuria is a genetic condition. Babies inherit it from their biological (birth) parents. To learn more about genetic conditions, visit MedlinePlus Genetics.
- Methylmalonic acidemia with homocystinuria is usually an autosomal recessive condition. Babies inherit the condition when each parent passes down the same nonworking gene that causes methylmalonic acidemia with homocystinuria (MMACHC, MMADHC, LMBRD1, or ABCD4) to their baby. Only babies with two matching nonworking genes—for example, one nonworking MMACHC from the mom and one nonworking MMACHC from the dad—have this condition. Babies with two nonworking genes that do not match—for example, one nonworking MMACHC from the mom and one nonworking LMBRD1 from the dad—will not have this condition.
- People with one working copy and one nonworking copy of the MMACHC, MMADHC, LMBRD1, or ABCD4 gene are called carriers.
- Carriers do not have or develop the condition. However, they may pass down a nonworking copy of the gene to their children.
- If two parents are carriers of a nonworking copy of the MMACHC, MMADHC, LMBRD1, or ABCD4 gene, they have a 1 in 4 chance of having a child with methylmalonic acidemia with homocystinuria.
- Carriers for methylmalonic acidemia with homocystinuria often do not know they are carriers before having a child with the condition. In most cases, families have no history of the condition until the birth of a child with methylmalonic acidemia with homocystinuria.
- Parents who already have a child with methylmalonic acidemia with homocystinuria due to a change in the MMACHC, MMADHC, LMBRD1, or ABCD4 gene still have a 1 in 4 chance of having another child with methylmalonic acidemia with homocystinuria. This 1 in 4 chance stays the same for all future children.
- In some cases, methylmalonic acidemia with homocystinuria is inherited in an X-linked recessive pattern. Babies inherit the condition on the X chromosome, which is one of the two sex chromosomes.
- When boys (who only have one X chromosome) receive one nonworking copy of the HCFC1 gene from their mom, they have this condition. Dads cannot pass on this condition to their sons.
- Because this condition is linked to the X chromosome, it is much more common in boys than girls. The condition is also usually more severe in boys than in girls.
- Genetic counselors and medical geneticists can help families learn about this condition and the chance of having children with it. Visit the National Society of Genetic Counselors to find a genetic counselor and the American College of Medical Genetics and Genomics to find a medical geneticist.
Treatment and Management
It is important to talk to your health care provider about which treatment(s) are best for your baby. The goal of treatment is to prevent the health problems caused by this condition.
Treatments may include the following:
- Vitamin B-12 treatments
- L-carnitine supplements
- Betaine supplements
- Low-protein diet
- Special formulas
- Frequent feedings to avoid long periods without food
Children who receive early and ongoing treatment for methylmalonic acidemia with homocystinuria can have healthy growth and development.