Beta ketothiolase deficiency

Title

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Other Names:

Alpha-methylacetoaceticaciduria; 2-methyl-3-hydroxybutyricacidemia; Mitochondrial acetoacetyl-CoA Thiolase deficiency; Alpha-methylacetoaceticaciduria; 2-methyl-3-hydroxybutyricacidemia; Mitochondrial acetoacetyl-CoA Thiolase deficiency; 3-oxothiolase deficiency; 3-ketothiolase deficiency See More

Categories:

Congenital and Genetic Diseases; Metabolic disorders; Newborn Screening

Summary Summary

Beta-ketothiolase deficiency is an inherited disorder in which the body cannot effectively process a protein building block (amino acid) called isoleucine. This condition also impairs the body's ability to process ketones, which are molecules produced during the breakdown of fats. Signs and symptoms typically appear between the ages of 6 and 24 months. Affected children experience intermittent episodes of ketoacidosis, characterized by vomiting, dehydration, difficulty breathing, extreme tiredness (lethargy), and occasionally, seizures. In severe cases, these episodes can lead to coma.^[1]^[2]^[3] Metabolic stroke is another finding that has been increasingly reported in children with this condition.^[2] Ketoacidotic attacks are frequently triggered by infections, periods without food (fasting), or increased intake of protein-rich foods.^[1]^[2]

Beta ketothiolase deficiency is inherited in an autosomal recessive fashion and is caused by pathogenic variants (mutations) in the ACAT1 gene.^[1]^[2]^[3] Treatment involves managing acute crises with intravenous (IV) fluids, glucose, and electrolytes along with bicarbonate. Long-term management involves eating frequently, following a reduced-protein diet, avoidance of high-fat foods, and, in some cases, carnitine supplementation.^[3]

Last updated: 6/28/2017

Symptoms Symptoms

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.

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Medical Terms	Other Names	Learn More: HPO ID
80%-99% of people have these symptoms
Fever		0001945
Hyperuricemia	High blood uric acid level	0002149
Ketonuria		0002919
Metabolic acidosis		0001942
Tachypnea	Increased respiratory rate or depth of breathing	0002789
Vomiting	Throwing up	0002013
30%-79% of people have these symptoms
Apathy	Lack of feeling, emotion, interest	0000741
Coma		0001259
Cough	Coughing	0012735
Dehydration		0001944
Diarrhea	Watery stool	0002014
Excessive daytime somnolence	Excessive daytime sleepiness More than typical sleepiness during day [ more ]	0001262
Hyperammonemia	High blood ammonia levels	0001987
Ketoacidosis		0001993
Leukocytosis	Elevated white blood count High white blood count Increased blood leukocyte number [ more ]	0001974
Thrombocytosis	Increased number of platelets in blood	0001894
5%-29% of people have these symptoms
Abnormal metabolic brain imaging by MRS		0012705
Agitation		0000713
Anorexia		0002039
Ataxia		0001251
Body odor		0500001
Edema	Fluid retention Water retention [ more ]	0000969
Extrapyramidal dyskinesia		0007308
Hepatomegaly	Enlarged liver	0002240
Hyperglycemia	High blood sugar	0003074
Hypertension		0000822
Hypoglycemia	Low blood sugar	0001943
Hyporeflexia	Decreased reflex response Decreased reflexes [ more ]	0001265
Hypotension	Low blood pressure	0002615
Increased serum lactate		0002151
Motor delay		0001270
Muscular hypotonia	Low or weak muscle tone	0001252
Oral aversion		0012523
Pallor		0000980
Seizure		0001250
Spasticity	Involuntary muscle stiffness, contraction, or spasm	0001257
Weight loss		0001824
1%-4% of people have these symptoms
Intellectual disability, mild	Mental retardation, borderline-mild Mild and nonprogressive mental retardation Mild mental retardation [ more ]	0001256
Intellectual disability, severe	Early and severe mental retardation Mental retardation, severe Severe mental retardation [ more ]	0010864
Percent of people who have these symptoms is not available through HPO
Autosomal recessive inheritance		0000007
Episodic ketoacidosis		0005974
Intellectual disability	Mental deficiency Mental retardation Mental retardation, nonspecific Mental-retardation [ more ]	0001249

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Last updated: 1/1/2021

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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.

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.

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.

Related Diseases Related Diseases

Related diseases are conditions that have similar signs and symptoms. A health care provider may consider these conditions in the table below when making a diagnosis. Please note that the table may not include all the possible conditions related to this disease.

Conditions with similar signs and symptoms from Orphanet
The differential diagnosis includes sepsis, other organic acidurias such as HSD10 disease and succinyl-CoA:3-ketoacid CoA transferase deficiency (see these terms), other conditions that cause ketoacidosis in childhood, and glycogen storage disease due to glycogen synthase deficiency (see this term). Visit the Orphanet disease page for more information.

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

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
MitoAction
PO Box 51474
Boston, MA 02205
Toll-free: 1-888-648-6228
Telephone: 1-888-MITO-411 (648-6411) for support line
E-mail: info@mitoaction.org
Website: https://www.mitoaction.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/

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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

Genetics Home Reference (GHR) contains information on Beta ketothiolase deficiency. This website is maintained by the National Library of Medicine.
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.
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 Beta ketothiolase deficiency. Click on the link to view a sample search on this topic.

Selected Full-Text Journal Articles

Abdelkreem E, Alobaidy H, Aoyama Y, Mahmoud S, Abd El Eal M, Fukao T. Two Libyan siblings with beta-ketothiolase deficiency: A case report and review of literature. Egyptian Jounral of Medical Human Genetics. April 2017; 18(2):199-203.
Akella RRD, Aoyama Y, Mori C, Lingappa L, Cariappa R, Fukao T. Metabolic encephalopathy in beta-ketothiolase deficiency: The first report from India. Brain Dev. Jun 2014; 36(6):537-40.

GARD Answers GARD Answers

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A young family has a 3 year old girl with this disease. The parents would like to have additional children but are afraid to have another affected baby. What are their options? See answer

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References References

Beta-ketothiolase deficiency. Genetics Home Reference. January 2008; http://ghr.nlm.nih.gov/condition/beta-ketothiolase-deficiency.
Abdelkreema E, Alobaidyc H, Aoyamad Y, Mahmoudb S, Abd El Aalb M, Fukao T. Two Libyan siblings with beta-ketothiolase deficiency: A case report and review of literature. Egyptian Journal of Medical Human Genetics. April 2017; 18(2):199-203. http://www.sciencedirect.com/science/article/pii/S1110863016300763.
Fukao T. Beta-ketothiolase deficiency. Orphanet. February 2015; http://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=en&Expert=134.

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