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Living with a Cobalamin Cofactor Metabolism Defect

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Living with a Cobalamin Cofactor Metabolism Defect Living with a Cobalamin Cofactor Metabolism Defect This brochure will help you understand the different types of cobalamin cofactor metabolism defects that cause homocystinuria, how they affect your body, and how you can manage your condition A few words about this brochure What is homocystinuria? Has your doctor diagnosed you or your child You may be reading this brochure because You may have heard the word “homocystinuria” with a cobalamin (co-BAL-uh-min) cofactor you have a cobalamin cofactor metabolism for the first time when your doctor talked metabolism defect? Cobalamin cofactor defect or because your child or a sibling to you about possibly having a cbl defect. metabolism defects are one of three types of or a friend has one. Or perhaps you’re Homocystinuria caused by cbl defects is the genetic disorders that cause homocystinuria a healthcare professional. Please note name for a group of rare disorders involving the (HO-mo-SIS-tin-YUR-ee-uh). The information the brochure addresses “you,” but it’s amino acid homocysteine (HO-mo-SIS-teen). in this brochure will help you understand understood that “you,” the reader, may not Amino acids are building blocks that your body these defects and how you can manage have a cobalamin cofactor metabolism uses to make proteins. Homocystinuria occurs your condition. defect yourself. when there is a buildup of homocysteine in your blood and urine. High levels of homocysteine For the remainder of this brochure, can be harmful to your body. cobalamin (cbl) cofactor metabolism defects will be referred to as cbl defects. How does homocysteine get in your body? It starts with the foods you eat. Your body makes homocysteine from another amino acid called methionine (meh-THIGH-uh-neen). Most foods contain some methionine. But high-protein foods such as meat, fish, eggs, or cheese tend to have the most methionine. Plant-based foods such as beans, tofu, and nuts also have higher amounts of methionine. So when you eat these types of foods, more methionine enters your body. Then your body breaks down – or metabolizes – the methionine you’ve eaten into homocysteine. 2 3 How do cbl defects cause homocystinuria? Are there different types of cbl defects? Since too much homocysteine can harm However, the process can break down if: Yes – there are many types of cbl a certain enzyme reaction cannot take place. your body, it needs to convert some of the defects. Each type is named with a This results in the buildup of a substance called - Your body cannot successfully homocysteine back to methionine. This different letter of the alphabet. The methylmalonic (MEH-thul-muh-LON-ik) acid complete the steps to produce enough process involves cobalamin – also called type of cbl defect you have depends on (MMA) that your body makes when it digests methylcobalamin. vitamin B12—that you get from the foods you what gene is affected and where the protein. High levels of MMA in your blood can eat. Your body goes through a series of steps - Your body cannot produce the enzymes process breaks down. Some cbl defects cause harmful symptoms to develop. This to convert vitamin B12 into methylcobalamin it needs for the chemical reaction to occur, also cause a second disorder along condition is called methylmalonic acidemia. (MEH-thul-co-BAL-uh-min). This is the form or your body makes enzymes that do not with homocystinuria. These are called of cobalamin that your body needs to convert work properly. “combined disorders.” Individuals who have a combined disorder homocysteine back to methionine. have both homocystinuria and methylmalonic Why would this happen? Your body uses Combined disorders acidemia. Both disorders can cause serious When the process is working the way it many genes to convert cobalamin to health problems. should, your body uses methylcobalamin methylcobalamin and to make the enzymes Combined disorders occur in people who and a few enzymes to convert homocysteine that are needed to complete this process. cannot successfully complete the steps back to methionine. Enzymes are proteins If something is wrong with any of these to produce enough methylcobalamin CblC defect is the most common genes, then the process can break down. and also a second form of cobalamin that help chemical reactions take place in cbl defect. About 1 in every 100,000 the body. that your body needs. These disorders If any step in the process does not occur, are known as: cblC defect (cblC), cblD babies is born with cblC defect then your body cannot convert homocysteine defect (cblD), cblF defect (cblF), cblJ in the United States. back to methionine through this pathway. defect (cblJ), and cblX defect (cblX). This causes homocysteine to build up in your body. It also causes methionine to decrease. When your body undergoes the steps Both can lead to serious health problems. to make methylcobalamin, it uses many of the same steps to help make a second type of cobalamin called adenosylcobalamin (uh-DEEN-oh-sil- co-BAL-uh-min). When your body does not produce enough adenosylcobalamin, 4 5 Are there different types of cbl defects? Why do you have a cbl defect? Single disorders Cbl defects are genetic disorders, which is another way of saying that the conditions Homocystinuria without methylmalonic Methylmalonic acidemia without are inherited from your parents. How you acidemia occurs when a person’s body homocystinuria occurs when a person does inherited your disorder depends on the cannot complete the final steps in the not produce enough adenosylcobalamin. specific type of cbl defect you have. Since process to produce methylcobalamin, or a These disorders are known as: cblA defect homocystinuria due to cbl defects is caused person’s body does not properly produce (cblA), cblB defect (cblB), and cblD defect by genetics, it is a lifelong condition. an enzyme that is needed to interact with variant 2 (cblD variant 2). These cbl defects methylcobalamin. These disorders are known will not be covered any further in this brochure. Inheritance pattern for all as: cblD defect variant 1 (cblD variant 1), cbl cblX The different types of cbl defects affect defects except cblE defect (cblE), and cblG defect (cblG). the body in different ways and can lead Cbl defects (except cblX) occur when you to different symptoms. Knowing the type inherit two copies of an abnormal variation of cbl defect you have is important for of a specific gene, one from each parent. developing a treatment plan that will help The medical term for this kind of inheritance you manage homocysteine, methionine, and is autosomal recessive. methylmalonic acid (MMA) levels in your If you have homocystinuria due to a cbl body on a day-to-day basis. defect and your parents do not, then they are carriers of the condition. This means they have one normal copy and one abnormal variation of the affected gene. They don’t have homocystinuria because their normal copy of the gene is able to keep their homocysteine levels at normal levels. 6 7 Brandon Nicole Unaffected Unaffected Why do you have a cbl defect? “carrier” “carrier” R r R r As an example, this diagram Inheritance pattern for cblX defect shows how homocystinuria R R R r R r r r due to cblC defect may affect CblX defect is caused by an abnormal Females have two X chromosomes. If a families. CblC defect is due variation in the HCFC1 gene, which is female inherits two abnormal HCFC1 genes, to an abnormal variation in located on the X chromosome. CblX one from each parent, then she will have cblX a gene called MMACHC. defect follows X-linked recessive defect. However, if a female inherits only one This gene helps convert inheritance in families. X-linked genes abnormal gene on the X chromosome from vitamin B12 that you get affect males and females differently. either her mother or her father, then she is a from the foods you eat into carrier of the condition. She is not likely to Males have one X and one Y methylcobalamin, the form Angela Justin Brianna Anthony have any symptoms of the disorder, or if she chromosome. If a male inherits an of cobalamin that your Unaffected Unaffected “carrier” Affected does, they are not likely to be severe. This is 1 in 4 chance 2 in 4 chance 1 in 4 chance abnormal HCFC1 gene on the X body needs. because her second copy of the HCFC1 gene chromosome from his mother, then he is usually working the way it should. will have cblX defect. He cannot inherit cblX defect from his father, even if his father has cblX defect, since he inherits a Y chromosome from his father. In this family, the parents, Brandon and Both of them could potentially pass on the Nicole, are carriers of cblC defect. Each affected gene to their future children. Angela child in the family has a 1 in 4 chance of has two normal copies of the gene. She will having cblC defect. In this case, Anthony, pass on a normal copy of the gene to any their son, has cblC defect because he future children that she has. inherited two abnormal variations of Being a carrier of homocystinuria due the MMACHC gene. The other children to cblC defect is much more common – Brianna, Justin, and Angela – do not than having the condition. That’s why have cblC defect. But Brianna and Justin many people who are diagnosed with cblC are carriers of the defect because they defect have no known family history of have one normal copy and one abnormal homocystinuria or methylmalonic acidemia. variation of the MMACHC gene.
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