Rare Oncology News

Disease Profile

Beta ketothiolase deficiency

Prevalence
Prevalence estimates on Rare Medical Network websites are calculated based on data available from numerous sources, including US and European government statistics, the NIH, Orphanet, and published epidemiologic studies. Rare disease population data is recognized to be highly variable, and based on a wide variety of source data and methodologies, so the prevalence data on this site should be assumed to be estimated and cannot be considered to be absolutely correct.

Unknown

Age of onset

Infancy

ageofonset-infancy.svg

ICD-10

E71.1

Inheritance

Autosomal dominant A pathogenic variant in only one gene copy in each cell is sufficient to cause an autosomal dominant disease

no.svg

Autosomal recessive Pathogenic variants in both copies of each gene of the chromosome are needed to cause an autosomal recessive disease and observe the mutant phenotype

rnn-autosomalrecessive.svg

X-linked
dominant X-linked dominant inheritance, sometimes referred to as X-linked dominance, is a mode of genetic inheritance by which a dominant gene is carried on the X chromosome.

no.svg

X-linked
recessive Pathogenic variants in both copies of a gene on the X chromosome cause an X-linked recessive disorder

no.svg

Mitochondrial or multigenic Mitochondrial genetic disorders can be caused by changes (mutations) in either the mitochondrial DNA or nuclear DNA that lead to dysfunction of the mitochondria and inadequate production of energy.

no.svg

Multigenic or multifactor Inheritance involving many factors, of which at least one is genetic but none is of overwhelming importance, as in the causation of a disease by multiple genetic and environmental factors.

no.svg

Not applicable

no.svg

Other names (AKA)

Alpha-methylacetoaceticaciduria; 2-methyl-3-hydroxybutyricacidemia; Mitochondrial acetoacetyl-CoA Thiolase deficiency;

Categories

Congenital and Genetic Diseases; Metabolic disorders; Newborn Screening

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]

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.

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

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.

    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

      Organizations Providing General Support

        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

              References

              1. Beta-ketothiolase deficiency. Genetics Home Reference. January 2008; https://ghr.nlm.nih.gov/condition/beta-ketothiolase-deficiency.
              2. 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. https://www.sciencedirect.com/science/article/pii/S1110863016300763.
              3. Fukao T. Beta-ketothiolase deficiency. Orphanet. February 2015; https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=en&Expert=134.