Conditions Methylmalonic Acidemia with Homocystinuria
Methylmalonic acidemia is an inherited condition in which the body is unable to process certain fats and proteins. It is considered an organic acid condition because it can lead to a harmful excess of certain toxins and organic acids. Methylmalonic acidemia with homocystinuria (Cbl C, D, F) is one type of methylmalonic acidemia. Individuals with this form of methylmalonic acidemia have trouble producing certain cobalamin enzymes, which causes harmful levels of homocysteine and methylmalonic acid to build up in their bodies.
There are other forms of methylmalonic acidemia that occur without homocystinuria. The different types of methylmalonic acidemia have different causes and treatments. To learn about other types of methylmalonic acidemia, read about methylmalonic acidemia caused by methylmalonyl-CoA mutase deficiencies or about methylmalonic acidemia caused by cobalamin deficiencies A and B.
Organic Acid Conditions
Methylmalonic acidemia is estimated to affect one out of every 50,000 to 100,000 individuals. However, methylmalonic acidemia with homocystinuria is only one form of methylmalonic acidemia, and the exact number of people affected by this specific form is currently unknown.
Also known as
- Cbl C, D, F
- Type 2 vitamin B12 metabolic defect
- Methyltetrahydrofolate methyltransferase deficiency
- Combined deficiency of methylmalonyl CoA mutase and homocystinuria
Your baby’s doctor may ask you if your baby is showing any of the signs of Cbl C, D, F (see Early Signs, below). If your baby has certain signs, your baby’s doctor may suggest starting immediate treatment.
If your baby’s newborn screening result for methylmalonic acidemia with homocystinuria (Cbl C, D, F) was out of the normal range, your baby’s doctor or the state screening program will contact you to arrange for your baby to have additional testing. It is important to remember that an out-of-range screening result does not necessarily mean that your child has the condition. An out-of-range result may occur because the initial blood sample was too small or the test was performed too early. However, a few babies do have the condition, so it is very important that you go to your follow-up appointment for a confirmatory test. Because the harmful effects of untreated Cbl C, D, F can occur soon after birth, follow-up testing must be completed as soon as possible to determine whether or not your baby has the condition.
Follow-up testing will involve checking your baby’s urine and blood samples for harmful levels of acids and toxins. Certain acids and toxins build up in the body when a child has an organic acid condition, so studying the levels of these substances in your baby’s body can help doctors determine if your baby has a condition. High levels of a homocysteine in the blood and methylmalonic acid in the urine might signal that your baby has Cbl C, D, F. Sometimes follow-up testing may include testing a very small sample of skin.
About Methylmalonic Acidemia with Homocystinuria
Signs of methylmalonic acidemia with homocystinuria (Cbl C, D, F) could begin anywhere between the first few days of life and 14 years of age. Children with Cbl C usually show symptoms between the first few days and the first month of life. Children with Cbl D deficiency do not show signs until later in childhood.
If your baby has Cbl C, D, F, you might notice signs including:
- Delayed growth
- Small head size
- Skin rash
- Poor appetite
- Sleeping longer or more often
- Weak muscle tone (called hypotonia)
Many of these signs may occur when your baby eats foods that their body cannot break down. They can be triggered by long periods of time without eating, illnesses, and infections.
If your baby shows any of these signs, be sure to contact your baby’s health care provider immediately.
Your baby will probably need to be on a restricted diet to avoid proteins that their body cannot break down. A dietician or nutritionist can help you plan a low-protein diet that still gives your baby the right nutrients for healthy growth.
Your baby’s doctor might recommend special formulas or foods especially for children with methylmalonic acidemia with homocystinuria (Cbl, C, D, F). These formulas will likely need to continue through adulthood.
Eating often will also help prevent your baby from experiencing many of the signs mentioned in the Early Signs section. Illnesses and infections can also trigger these signs.
Supplements and Medications
Natural supplements can also help treat Cbl C, D, F. Vitamin B-12 can help reduce the signs and symptoms of the condition in some children. Your baby’s doctor may need to try this treatment for a short period of time in order to determine if it is an effective treatment for your baby. Talk to your baby’s doctor before starting vitamin B-12 treatment.
L-carnitine is another natural substance that helps get rid of harmful waste products in the body. Some babies do not need this supplement, but your baby’s body might not be making enough carnitine naturally. Your baby’s doctor can tell you if you baby needs these supplements and write an appropriate prescription.
Betaine supplements can help lower acid levels in your baby’s blood. While everyone has some acid in their blood, high levels can be toxic. Betaine is a healthy substance found naturally in many foods. Your baby’s doctor can write you a prescription for these supplements.
Since methylmalonic acidemia with homocystinuria (Cbl C, D, F) is rare, it is not yet certain how effective these dietary and supplement treatments are (see Treatment). It has been recognized that treatments helped some children avoid the signs and symptoms of the condition, whereas they did not help other children.
It is possible for children with the condition to have learning disabilities, intellectual disabilities, or other complications, even with treatment.
When we eat food, enzymes help break it down. Certain enzymes break down proteins into their building blocks, amino acids. Other enzymes break down these amino acids.
Some enzymes need help from vitamins like vitamin B-12 (also called cobalamin). The enzymes that break down the amino acids isoleucine, valine, methionine, and threonine need vitamin B-12 to work correctly.
If your baby has methylmalonic acidemia with homocystinuria (Cbl C, D, F), their body cannot use vitamin B-12 correctly. Your baby’s body either does not make enough or makes non-working enzymes that are supposed to turn vitamin B-12 from food into a form that the body can use.
Cbl C, D, F is an autosomal recessive genetic condition. This means that a child must inherit two copies of the non-working gene for Cbl C, D, F, one from each parent, in order to have the condition. The parents of a child with an autosomal recessive condition each carry one copy of the non-working gene, but they typically do not show signs and symptoms of the condition. While having a child with Cbl C, D, F is rare, when both parents are carriers, they can have more than one child with the condition. Learn more about autosomal recessive inheritance.
Support for Methylmalonic Acidemia with Homocystinuria
Support groups can help connect families who have a child or other family member affected by methylmalonic acidemia with a supportive community of people who have experience and expertise in living with the condition. These organizations offer resources for families, affected individuals, health care providers, and advocates.
Work with your baby’s doctor to determine the next steps for your baby’s care. Your baby’s doctor may help you coordinate care with a physician who specializes in metabolism, a dietician who can help plan your child’s specialized diet, or other medical resources in your community. Some children with methylmalonic acidemia with homocystinuria (Cbl C, D, F) have developmental delays. If you think that your baby is not meeting their developmental milestones, ask your baby’s doctor about the next steps in accessing a developmental evaluation and care.
Because Cbl C, D, F is a genetic condition, you may want to talk with a genetics specialist. A genetic counselor or geneticist can help you understand the causes of the condition, discuss genetic testing for methylmalonic acidemia with homocystinuria, and understand what this diagnosis means for other family members and future pregnancies. Speak with your baby’s doctor about getting a referral. The Clinic Services Search Engine offered by the American College of Medical Genetics and Genomics (ACMG) and the Find a Genetic Counselor tool on the National Society of Genetic Counselors (NSGC) website are two good resources for you or your baby's health care provider to use to identify local specialists.