Isovaleric acidemia

Title

Other Names:

Isovaleric acid CoA dehydrogenase deficiency; IVA; Isovaleryl CoA carboxylase deficiency; Isovaleric acid CoA dehydrogenase deficiency; IVA; Isovaleryl CoA carboxylase deficiency; IVD deficiency See More

Categories:

Congenital and Genetic Diseases; Metabolic disorders; Newborn Screening

Summary Summary

Isovaleric acidemia (IVA) is a type of organic acid disorder in which affected individuals have problems breaking down an amino acid called leucine from the food they eat.^[1]^[2] Signs and symptoms may range from very mild to life-threatening. In severe cases, symptoms begin within a few days of birth and include poor feeding, vomiting, seizures, and lack of energy (lethargy); these may progress to more serious medical problems including seizures, coma, and possibly death. In other cases, signs and symptoms appear during childhood and may come and go over time. A characteristic sign of IVA is a distinctive odor of sweaty feet during acute illness. Other features may include failure to thrive or delayed development. IVA is caused by mutations in the IVD gene and is inherited in an autosomal recessive manner.^[1] Treatment involves moderate restriction of proteins in the diet and oral administration of glycine and L-carnitine which helps to rid the body of excess isovaleric acid.^[2]^[3]^[4]

Last updated: 5/16/2014

Symptoms Symptoms

Health problems related to isovaleric acidemia range from very mild to life-threatening. In severe cases, the features of isovaleric acidemia become apparent within a few days after birth. The initial symptoms include poor feeding, vomiting, seizures, and lack of energy (lethargy). These symptoms sometimes progress to more serious medical problems, including seizures, coma, and possibly death. A characteristic sign of isovaleric acidemia is a distinctive odor of sweaty feet during acute illness. This odor is caused by the buildup of a compound called isovaleric acid in affected individuals.^[1]^[4]

In other cases, the signs and symptoms of isovaleric acidemia appear during childhood and may come and go over time. Children with this condition may fail to gain weight and grow at the expected rate (failure to thrive) and often have delayed development. In these children, episodes of more serious health problems can be triggered by prolonged periods without food (fasting), infections, or eating an increased amount of protein-rich foods.^[1]

Some people with gene mutations that cause isovaleric acidemia are asymptomatic, which means they never experience any signs or symptoms of the condition.^[1]

Last updated: 5/16/2014

This table lists symptoms that people with this disease may have. For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed. This information comes from a database called the Human Phenotype Ontology (HPO) . The HPO collects information on symptoms that have been described in medical resources. The HPO is updated regularly. Use the HPO ID to access more in-depth information about a symptom.

Showing of 15 |

Medical Terms	Other Names	Learn More: HPO ID
80%-99% of people have these symptoms
Global developmental delay		0001263
Metabolic acidosis		0001942
30%-79% of people have these symptoms
Seizures	Seizure	0001250
5%-29% of people have these symptoms
Cerebellar hemorrhage		0011695
Percent of people who have these symptoms is not available through HPO
Autosomal recessive inheritance		0000007
Bone marrow hypocellularity	Bone marrow failure	0005528
Coma		0001259
Dehydration		0001944
Hyperglycinuria	High urine glycine levels	0003108
Ketoacidosis		0001993
Lethargy		0001254
Leukopenia	Decreased blood leukocyte number Low white blood cell count [ more ]	0001882
Pancytopenia	Low blood cell count	0001876
Thrombocytopenia	Low platelet count	0001873
Vomiting	Throwing up	0002013

Showing of 15 |

Do you have more information about symptoms of this disease? We want to hear from you.

Last updated: 12/1/2019

Do you have updated information on this disease? We want to hear from you.

Cause Cause

Isovaleric acidemia is caused by mutations in the IVD gene. The IVD gene provides instructions for making an enzyme that plays an essential role in breaking down proteins from the diet. Specifically, this enzyme helps process the amino acid leucine, which is part of many proteins. If a mutation in the IVD gene reduces or eliminates the activity of this enzyme, the body is unable to break down leucine properly. As a result, an organic acid called isovaleric acid and related compounds build up to harmful levels in the body. This buildup damages the brain and nervous system, causing serious health problems.^[1]

Last updated: 5/16/2014

Inheritance Inheritance

Isovaleric acidemia is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.^[1]

Last updated: 5/16/2014

Diagnosis Diagnosis

Making a diagnosis for a genetic or rare disease can often be challenging. Healthcare professionals typically look at a person’s medical history, symptoms, physical exam, and laboratory test results in order to make a diagnosis. The following resources provide information relating to diagnosis and testing for this condition. If you have questions about getting a diagnosis, you should contact a healthcare professional.

Testing Resources

The Genetic Testing Registry (GTR) provides information about the genetic tests for this condition. The intended audience for the GTR is health care providers and researchers. Patients and consumers with specific questions about a genetic test should contact a health care provider or a genetics professional.

Newborn Screening

An ACTion (ACT) sheet is available for this condition that describes the short-term actions a health professional should follow when an infant has a positive newborn screening result. ACT sheets were developed by experts in collaboration with the American College of Medical Genetics.
An Algorithm flowchart is available for this condition for determining the final diagnosis in an infant with a positive newborn screening result. Algorithms are developed by experts in collaboration with the American College of Medical Genetics.
Baby's First Test is the nation's newborn screening education center for families and providers. This site provides information and resources about screening at the local, state, and national levels and serves as the Clearinghouse for newborn screening information.
The Newborn Screening Coding and Terminology Guide has information on the standard codes used for newborn screening tests. Using these standards helps compare data across different laboratories. This resource was created by the National Library of Medicine.
National Newborn Screening and Global Resource Center (NNSGRC) provides information and resources in the area of newborn screening and genetics to benefit health professionals, the public health community, consumers and government officials.

Treatment Treatment

There is currently no cure for isovaleric acidemia (IVA). Upon diagnosis, immediate treatment is typically necessary in order to prevent metabolic crises and complications that may follow. It is often recommended that affected individuals have a low-leucine / low-protein diet and use medical foods (such as special low-protein flours, pastas, and rice that are made especially for people with organic acid disorders) and leucine-free medical formula. A dietician with knowledge of IVA can help parents create a food plan that contains the right amount of protein, nutrients, and energy to keep the child healthy. Any diet changes should be under the guidance of a dietician. Medications that may be recommended include glycine and L-carnitine, which help rid the body of unwanted isovaleric acid and other harmful substances. No medication or supplement should be used without checking with a metabolic doctor. Children with symptoms of a metabolic crisis need medical treatment right away and may be given bicarbonate, glucose, and other medications by IV.^[2]

With prompt and careful treatment, children with IVA have a good chance to live healthy lives with normal growth and development. However, some children, even when treated, may have repeated metabolic crises which can lead to life-long learning problems or intellectual disability.^[2]

Last updated: 5/16/2014

Management Guidelines

Orphanet Emergency Guidelines is an article which is expert-authored and peer-reviewed that is intended to guide health care professionals in emergency situations involving this condition.

Find a Specialist Find a Specialist

If you need medical advice, you can look for doctors or other healthcare professionals who have experience with this disease. You may find these specialists through advocacy organizations, clinical trials, or articles published in medical journals. You may also want to contact a university or tertiary medical center in your area, because these centers tend to see more complex cases and have the latest technology and treatments.

If you can’t find a specialist in your local area, try contacting national or international specialists. They may be able to refer you to someone they know through conferences or research efforts. Some specialists may be willing to consult with you or your local doctors over the phone or by email if you can't travel to them for care.

You can find more tips in our guide, How to Find a Disease Specialist. We also encourage you to explore the rest of this page to find resources that can help you find specialists.

Healthcare Resources

To find a medical professional who specializes in genetics, you can ask your doctor for a referral or you can search for one yourself. Online directories are provided by the American College of Medical Genetics and the National Society of Genetic Counselors. If you need additional help, contact a GARD Information Specialist. You can also learn more about genetic consultations from Genetics Home Reference.

Organizations Organizations

Support and advocacy groups can help you connect with other patients and families, and they can provide valuable services. Many develop patient-centered information and are the driving force behind research for better treatments and possible cures. They can direct you to research, resources, and services. Many organizations also have experts who serve as medical advisors or provide lists of doctors/clinics. Visit the group’s website or contact them to learn about the services they offer. Inclusion on this list is not an endorsement by GARD.

Organizations Supporting this Disease

MEBO Research: Systemic Body Odor and Halitosis
Toll-free: 0800 0588015 (UK)
Telephone: +1-786-228-6880 (USA)
E-mail: info@meboresearch.org
Website: https://meboresearch.org/
Metabolic Support UK
5 Hilliards Court
Sandpiper Way
Chester Business Park
Chester, CH4 9QP United Kingdom
Toll-free: 0800 652 3181
Telephone: 0845 241 2173
E-mail: https://www.metabolicsupportuk.org/contact-us
Website: https://www.metabolicsupportuk.org
Organic Acidemia Association
9040 Duluth Street
Golden Valley, MN 55427
Telephone: 763-559-1797
Fax: 866-539-4060
E-mail: mkstagni@gmail.com
Website: http://www.oaanews.org/

Do you know of an organization? We want to hear from you.

Learn More Learn More

These resources provide more information about this condition or associated symptoms. The in-depth resources contain medical and scientific language that may be hard to understand. You may want to review these resources with a medical professional.

Where to Start

Baby's First Test offers an information page on Isovaleric acidemia.
Genetics Home Reference (GHR) contains information on Isovaleric acidemia. This website is maintained by the National Library of Medicine.
The National Organization for Rare Disorders (NORD) has a report for patients and families about this condition. NORD is a patient advocacy organization for individuals with rare diseases and the organizations that serve them.
The Screening, Technology And Research in Genetics (STAR-G) Project has a fact sheet on this condition, which was written specifically for families that have received a diagnosis as a result of newborn screening. This fact sheet provides general information about the condition and answers questions that are of particular concern to parents.

In-Depth Information

The Monarch Initiative brings together data about this condition from humans and other species to help physicians and biomedical researchers. Monarch’s tools are designed to make it easier to compare the signs and symptoms (phenotypes) of different diseases and discover common features. This initiative is a collaboration between several academic institutions across the world and is funded by the National Institutes of Health. Visit the website to explore the biology of this condition.
The New England Consortium of Metabolic Program has written medical guidelines called acute care protocols for Isovaleric acidemia for health care professionals.
Online Mendelian Inheritance in Man (OMIM) is a catalog of human genes and genetic disorders. Each entry has a summary of related medical articles. It is meant for health care professionals and researchers. OMIM is maintained by Johns Hopkins University School of Medicine.
Orphanet is a European reference portal for information on rare diseases and orphan drugs. Access to this database is free of charge.
PubMed is a searchable database of medical literature and lists journal articles that discuss Isovaleric acidemia. Click on the link to view a sample search on this topic.

GARD Answers GARD Answers

Questions sent to GARD may be posted here if the information could be helpful to others. We remove all identifying information when posting a question to protect your privacy. If you do not want your question posted, please let us know. Submit a new question

My child was diagnosed with isovaleric acidemia and is currently being treated with carnitine three times daily. I wanted to know if there were cures for this disease. See answer
My grandson was diagnosed with IVA at birth. He seems to be quite healthy. He's 8 years old, very active and grades are great at school. His diet is mostly potatoes and fruit. He will not eat meat or poultry, but on some occasions. Will this condition be with him throughout his life, or is it possible that it will clear up? See answer
My baby died 13 days after birth. The doctors performed some blood tests which indicated that the baby had isovaleric acidemia. Additional testing, only available in the UK was recommended. Unfortunately, the lab would not accept blood without urine. What are the chances that my future child(ren) will also have this condition? See answer

Have a question? Contact a GARD Information Specialist.

References References

Isovaleric acidemia. Genetics Home Reference (GHR). 2007; http://www.ghr.nlm.nih.gov/condition/isovaleric-acidemia. Accessed 5/16/2014.
Organic Acid Oxidation Disorders: Isovaleric Acidemia. Screening, Technology and Research in Genetics (STAR-G). June 22, 2011; http://www.newbornscreening.info/Parents/organicaciddisorders/IVA.html. Accessed 5/16/2014.
Isovaleric acidemia. Orphanet. April 2014; http://www.orpha.net/consor/cgi-bin/OC_Exp.php?Lng=EN&Expert=33. Accessed 5/16/2014.
Babys First Test Isovaleric Acidemia. Baby's First Test. http://www.babysfirsttest.org/conditions/IVA. Accessed 5/16/2014.