2-Methyl-3-Hydroxybutyric acidemia (2M3HBA) Deficiency

If it is suspected that 2-methyl-3-hydroxybutyric acidemia (2M3HBA) deficiency was inherited, the mother of the child should be tested as she may not be showing many features of the deficiency. The siblings of a person who has the condition may also consider testing. Talk to your doctor or meet with a genetic counselor to better understand who in your family may need testing.

The Organic Acidemia Association place families in touch with other families with 2-methyl-3-hydroxybutyric acidemia (2M3HBA) deficiency, but the deficiency is extremely rare and it may be difficult to connect with other families with the same genetic disorder. While other individuals may have similar clinical features, each person is affected differently by the change in the HSD17B10 gene.

It is recommended that patients with for 2-methyl-3-hydroxybutyric acidemia (2M3HBA) deficiency see a genetic counselor or a geneticist. Patients with this syndrome should also be followed by a metabolic specialist to help monitor the individual’s diet. Regular vision and hearing screening can monitor for loss. People with seizures will need to be seen by a neurologist. Talk to your doctor about the specialists in your area.

It is important for children with 2-methyl-3-hydroxybutyric acidemia (2M3HBA) deficiency to be seen by a metabolic specialist. Physical therapy can also aid individuals with 2-methyl-3-hydroxybutyric acidemia (2M3HBA) deficiency who have low muscle tone. Regular hearing and vision screening is important to help treat hearing and vision loss. If a child has seizures, a neurologist may need to help treat the seizures. Other specialists may be needed if other health problems arise. Talk to your doctor about the specialists you can see in your area.

The usual abbreviations for 2-methyl-3-hydroxybutyric acidemia (2M3HBA) disease include:

2-methyl-3-hydroxybutyric acidemia (2M3HBA) deficiency is an inherited (genetic) disease that causes the body to not be able to break down a protein building block called isoleucine. Health problems with 2-methyl-3-hydroxybutyric acidemia (2M3HBA) deficiency are more severe in males than in females. In general males will have more health concerns than females because of how the gene is expressed. Males will generally start developing movement problems, seizures, and have general low muscle tone. Males often lose any motor milestones they develop while females generally only show development delays but no loss of milestones. Since there is progressive hearing and vision loss, taking steps to monitor and/or counteract the effects of the syndrome should be taken to better the quality of life. In addition, a special diet should be followed to help prevent some of the health problems but still get enough nutrition. Talk to your doctor about the best ways to monitor for hearing and vision loss and how to get connected with a metabolic specialist in your area.

The severity of health problems seen with 2-methyl-3-hydroxybutyric acidemia (2M3HBA) deficiency depends on if a person is a male or a female. In general, males will have more severe symptoms than females. Males start out with normal early development. However, before the age of 5 years, they start to loose milestones. So, if they were sitting, standing or walking, they loose the ability to do this (developmental regression). Males can have weak muscles (hypotonia), seizures, problems moving and intellectual disability (learning problems). It is also common to have vision and hearing loss as they get older. Females can have some of the same symptoms including learning problems, seizures and hearing loss. However, females do not usually have developmental regression. The reason that females tend to have less severe symptoms is because the gene is expressed differently in males than in females. Individuals with this condition should be monitored closely by their doctor or other appropriate specialists to monitor vision, hearing, seizures, learning and any additional health problems that may arise. Speak with your doctor about the specialists in your area.

Genes are the instructions that tell the body how to work. 2-methyl-3-hydroxybutyric acidemia (2M3HBA) deficiency is caused by changes in a gene called the HSD17B10 gene. The HSD17B10 gene gives instructions for you body to make a protein called HSD10. The change in the HSD17B10 gene leads to a change in the HSD10 protein. This protein is called an enzyme, which is a group of proteins that act to speed up a reaction within cells. In this case, this enzyme’s job is to break down the protein building block, isoleucine. This protein also breaks down fatty acids, and helps in the chemical reactions involving sex hormones. It also plays a role in regulating activity in the nervous system.
When a change occurs in our genes that leads to a change in this protein, the resulting protein is not able to do its job as efficiently, or not be able to do its job at all.
2M3HBA deficiency is inherited in an X-linked dominant pattern in families. Chromosomes provide the instructions that tell the body how to work correctly. Chromosomes come in pairs, and one member of the pair comes from the mother and the other member comes from the father. Twenty-two of the pairs are matching. The 23rd pair is called the sex chromosomes, because they determine the gender of an individual. Females have two copies of the X chromosome, and males have one X and one Y chromosome. The gene for 2M3HBA deficiency is found on the X chromosome. Having one copy of a gene change in this condition is sufficient to cause symptoms, thus females have symptoms. However, since males who have a gene change in the affected gene do not have a normal working copy, the symptoms tend to be more severe in males. If you or a family member has had genetic testing for 2-methyl-3-hydroxybutyric aciduria (2M3HBA) deficiency and you would like to learn more about the genetic change that was found, talk to your doctor or a genetic counselor in your area.

Genes are the instructions that tell the body how to work. 2-methyl-3-hydroxybutyric acidemia (2M3HBA) deficiency is caused by changes in a gene called the HSD17B10 gene. The HSD17B10 gene gives instructions for you body to make a protein called HSD10. The HSD10 protein has many jobs in the body. It is responsible for breaking down some fats and building blocks called isoleucine. It also plays a role maintaining the correct levels of male and female hormones. In addition, the HSD10 protein helps the brain function correctly. When there is a gene change in the HSD17B10 gene it causes the gene to either make less or no HSD10 protein. Researchers are unsure as of July 2016 why having less than normal amounts of this protein leads to the symptoms seen in 2-methyl-3-hydroxybutyric acidemia (2M3HBA) deficiency. If you or a family member have had genetic testing for 2-methyl-3-hydroxybutyric acidemia (2M3HBA) deficiency and you would like to learn more about the genetic change that was found, talk to your doctor or a genetic counselor in your area.

An inherited "variant" in the HSD17B10 gene for 2-methyl-3-hydroxybutyric acidemia (2M3HBA) deficiency means the individual has inherited a change in the gene that may cause the deficiency. A variant may or may not cause features of the syndrome. There are natural changes in every person walking around which is what makes everyone different. Other gene changes cause the body to work improperly and can cause disease. There are several different variants found to cause 2-methyl-3-hydroxybutyric acidemia (2M3HBA) deficiency. As of July 2016, conclusions have not been drawn pointing to different variants being "worse" or "better" than others. A genetic counselor or medical geneticist can help you understand more about a gene variant you may have.

A variant in the HSD17B10 gene for 2-methyl-3-hydroxybutyric acidemia (2M3HBA) deficiency means the individual has inherited a change in the HSD17B10 gene that causes the deficiency. A variant may or may not cause features of the syndrome. There are natural changes in every person walking around, it just so happens some changes cause genetic syndromes and others do not. There are variants in genes that do not cause the function of that gene to change and other changes that do influence the function of that gene, and that is when we see syndromes. There are several different variants found to cause 2-methyl-3-hydroxybutyric acidemia (2M3HBA) deficiency although it does not appear that different variants are "worse" or "better" than others. If you have had genetic testing for 2-methyl-3-hydroxybutyric acidemia (2M3HBA) deficiency and want to better understand your test results, talk to your doctor or a genetic counselor in your area.

The main symptoms of 2-methyl-3-hydroxybutyric acidemia (2M3HBA) deficiency will generally start to be noticeable in infancy and include:

As of July 2016, scientists are not aware of any individuals with a gene change (mutation) in the gene for 2-methyl-3-hydroxybutyric acidemia (2M3HBA) deficiency who does not have symptoms of the disorder. Therefore, the condition is 100% penetrant. However, we know that males have more severe symptoms than females. Therefore, there is variable expression of this condition. If you or a family member have had testing and are known to have a mutation in the gene for 2-methyl-3-hydroxybutyric acidemia (2M3HBA) deficiency, speaking with a medical geneticist or a genetic counselor in your area may help you understand more about the disease and the mutation in your family.

Newborn testing for 2-methyl-3-hydroxybutyric acidemia (2M3HBA) deficiency is available. In addition, if your doctor suspects that your child has this condition, testing can be done on blood and urine samples after birth to confirm this diagnosis. If your newborn has a positive newborn screen result, it does not mean there is a genetic condition present. However, it is very important to keep your appointments for follow-up testing so the newborn can start any treatment that is recommended as soon as possible.

There is only one form of 2-methyl-3-hydroxybutyric acidemia (2M3HBA) deficiency. However, there are different types of gene changes (mutations) that cause 2-methyl-3-hydroxybutyric acidemia (2M3HBA) deficiency. All mutations cause the gene to not work properly. However, some mutations can be found by looking at each "letter" in the gene. This is called gene sequencing. Other mutations are caused by parts of the gene being copied (duplicated) or missing (deleted). Your doctor or a genetic counselor in your area can help you understand the best type of genetic testing to have done.

As of March 2019, there were not any clinical research studies for 2-methyl-3-hydroxybutyric acidemia (2M3HBA) deficiency. The U.S. National Institutes of health maintains a website where you can find out if there are any current studies registered. You can access this information at the ClinicalTrials.gov link and type in 2-methyl-3-hydroxybutyric acidemia to search for current studies.

The treatment for 2-methyl-3-hydroxybutyric acidemia (2M3HBA) deficiency includes modifying the diet of the affected individual so they do not eat the protein building blocks the patient’s body cannot breakdown. A dietitian who specializes in treating metobolic disorders is helpful for patients with this syndrome. The American College of Medical Genetics can help you find a metabolic specialist in your area.

Because of how rare 2-methyl-3-hydroxybutyric acidemia (2M3HBA) deficiency is, nutrition is currently the only treatment for this syndrome. The doctor should know to follow the patient’s milestones, since intellectual delay has been documented, and ensure the patient should be seeing a metabolic specialist (nutritionist) regularly. Regular vision and hearing screening can monitor for loss. People with seizures will need to be seen by a neurologist. Talk to your doctor about the specialists in your area.

The prevalence of 2-methyl-3-hydroxybutyric acidemia (2M3HBA) deficiency is unknown. It is a very rare genetic disorder with a prevalence of less than 1 in 1 million people. To learn more about this disorder, visit Genetics Home Reference.

2-methyl-3-hydroxybutyric acidemia (2M3HBA) deficiency is inherited in an X-linked dominant manner. The genes in our body are the instructions that tell the body how to work correctly. Genes are organized onto structures called chromosomes. In most cells in our body, we have 46 chromosomes. The chromosomes come in pairs, with half of the chromosomes coming from the mother and half from the father. The first 22 pairs of chromosomes are matching. However, the 23rd pair of chromosomes is called the sex chromosomes, because that pair determines the gender of an individual. Females have two copies of the X chromosome, which means they have two copies of each of the genes found on the X chromosome. Males have one X chromosome and one Y chromosome. There are only a few genes that are the same on the X and Y chromosomes. The gene for 2-Methyl-3-Hydroxybutyric acidemia (2M3HBA) deficiency is only found on the X chromosome and not the Y chromosome. Therefore, males only have one copy of this gene. Therefore, if the gene that causes 2-methyl-3-hydroxybutyric acidemia (2M3HBA) deficiency has a genetic change (mutation) there is no "back up" gene like there is in females. For this reason, males have more severe symptoms than females.
If a female has a mutation in the gene for 2-Methyl-3-Hydroxybutyric acidemia (2M3HBA) deficiency, there is a 50% chance she will pass on the abnormal gene and thus the condition to her children with each pregnancy. Males with 2-Methyl-3-Hydroxybutyric acidemia (2M3HBA) deficiency will pass the condition on to all of their daughters and none of their sons. Meeting with a genetic counselor in your area can help you and other family members better understand their risks to have a child with 2-Methyl-3-Hydroxybutyric acidemia (2M3HBA) deficiency.

Global Gene’s toolkit offers information on how to start a support group for conditions such as 2-methyl-3-hydroxybutyric acidemia (2M3HBA) deficiency.

Newborn babies with 2-methyl-3-hydroxybutyric acidemia (2M3HBA) deficiency may have an abnormal newborn screening test. If so, doctors will need to also test your baby’s urine and blood. In some cases, they may also want to take a small sample of skin called a skin biopsy. If the diagnosis is confirmed by testing blood and urine, then your doctor may also discuss genetic (DNA) testing of the HSD17B10 gene. Speak with your doctor if you have questions about testing for 2-methyl-3-hydroxybutyric acidemia (2M3HBA) deficiency.

ClinicalTrials.gov is a website that includes all verified clinical trials currently accepting new patients for all syndromes. You can type 2-methyl-3-hydroxybutyric acidemia (2M3HBA) deficiency in the search box to look for clinical trials for this condition.

A "Clinic Services Search Engine" (http://www.ohsu.edu/xd/health/child-development-and-rehabilitation-center/clinics-and-programs/cdrc-portland-programs/metabolic-disorders-program/us-metabolic-clinics.cfm) has been designed for patients with acidemia to find specialists in their area. Because of how rare 2-methyl-3-hydroxybutyric acidemia (2M3HBA) deficiency is- there have only been 11 documented cases, it may be difficult to find a doctor that specializes in the deficiency.

To find out if a person has 2-methyl-3-hydroxybutyric acidemia (2M3HBA) deficiency, the doctor will need to have a blood and/or urine sample. For genetic (DNA) testing the preferred sample type to test for for 2-methyl-3-hydroxybutyric acidemia (2M3HBA) deficiency is peripheral blood. However, a sample from a skin biopsy could also be tested as the genetic information is the same in all most cells of the body. Your doctor or a genetic counselor in your area can help you understand the best type of testing to have done.

There are many different names for this 2-methyl-3-hydroxybutyric acidemia (2M3HBA) deficiency, including:

Males with 2-methyl-3-hydroxybutyric acidemia (2M3HBA) deficiency have developmental regression of motor skills, while females do not. Children with developmental regression will develop skills, such as sitting up or crawling. However, over time they lose the ability to do these things. If you have a child with this condition it is important to speak with your doctor to discuss how best to monitor your child’s development.

A support group that may be helpful in connecting other patients with 2-methyl-3-hydroxybutyric acidemia (2M3HBA) deficiency includes the Organic Acidemia Association (http://www.oaanews.org/) – a ThinkGenetic Advocacy Partner. Unfortunately, because the deficiency is so rare, connecting with a family with 2-methyl-3-hydroxybutyric acidemia (2M3HBA) deficiency may be difficult.

For 2-methyl-3-hydroxybutyric acidemia (2M3HBA) deficiency, there have been some cases where there seems to be a connection between the change in the HSD17B10 gene and the symptoms the patient first shows. There also have been cases where the same change results in varying degrees of severity. A visit with a medical geneticist in your area can help you learn more about this condition.