Beta-Ketothiolase Deficiency

Other Names


Alpha-methylacetoacetic aciduria

2-methyl-3-hydroxybutyric acidemia

Mitochondrial acetoacetyl-CoA thiolase (MAT) deficiency

3-ketothiolase deficiency

3-oxothiolase deficiency

Diagnosis Coding

E71.19, other disorders of branched-chain amino-acid metabolism

Disorder Category

An organic acidemia



Elevated C5-OH (2-methyl-3-hydroxybutyrylcarnitine), elevated C5:1 (tiglycarnitine)

Tested By

Tandem mass spectrometry (MS/MS); sensitivity=NA; specificity=NA


Due to absence of the enzyme mitochondrial acetoacetyl-CoA thiolase, patients are unable to break down the amino acid isoleucine. The breakdown of ketone bodies is also causing a buildup of organic acids and a decreased ability to generate energy. Patients typically present with metabolic acidosis induced by fasting, infection, fever or vomiting.


Autosomal recessive

Prenatal Testing

DNA testing possible by amniocentesis or chorionic villus sampling (CVS) if both disease causing mutations of an affected family member have been identified.

Other Testing

Genetic testing is possible for at-risk family members if both disease causing mutations of an affected family member have been identified.

Clinical Characteristics

With treatment, normal development can be expected with avoidance of severe recurrent metabolic crises. Without treatment, outcomes can vary widely due to broad clinical heterogeneity, with death or severe neurologic impairment possible, particularly in those with severe episodes in infancy. Age of symptom onset is variable, ranging from 3 days to 4 years, with the mean age at presentation of 15 months. Symptoms may be triggered by fasting and illness.

Initial signs/symptoms may include:
  • feeding problems
  • vomiting, possibly with hematemesis
  • diarrhea
  • lethargy progressing to coma
  • hypoglycemia or occasionally hyperglycemia

If not treated promptly, patients may experience:
  • acute metabolic acidosis
  • failure to thrive
  • intellectual disability
  • death

Follow-up Testing after Positive Screen

Quantitative plasma acylcarnitine profile, serum biotinidase assay, urine organic acids. Not all patients will have identifiable biochemical abnormalities at time of follow-up and DNA testing might be indicated.

Primary Care Management

Upon Notification of the + Screen

If the Diagnosis is Confirmed

  • Educate the family regarding signs, symptoms, and the need for urgent care when the infant becomes ill.
  • Avoidance of fasting; frequent, low protein, high carbohydrate meals. Uncooked cornstarch might be indicated in some cases.
  • Some patients tend to spontaneously restrict proteins as they get older.
  • Oral L-carnitine may be indicated for some affected children.
  • Bicarbonate and intravenous glucose may be indicated during metabolic crisis.
  • Monitor urine ketone levels when the child is sick or unable to eat.
  • For those identified after irreversible consequences, assist in management, particularly with developmental and educational interventions.

Specialty Care Collaboration

Initial consultation and ongoing collaboration, particularly for dietary management. Genetic counseling for the family.


Information & Support

For Professionals

Beta-Ketothiolase Deficiency - Information for Professionals (STAR-G)
Structured list of information about the condition and links to more information; Screening, Technology, and Research in Genetics.

ACT Sheet for Elevated C5-OH Acylcarnitine (ACMG) (PDF Document 400 KB)
Contains short-term recommendations for clinical follow-up of the newborn who has screened positive; American College of Medical Genetics.

Newborn Screening ACT Sheets & Confirmatory Algorithms (ACMG)
ACTion (ACT) Sheets and algorithms for responding to positive newborn screening test results, membership required; American College of Medical Genetics.

Resources for Beta-Ketothiolase deficiency (NLM)
Comprehensive compilation of links to information, articles, research, case studies, genetics, and more; from the National Library of Medicine and the Genetic Alliance.

Beta-Ketothiolase Deficiency (OMIM)
Extensive review of literature that provides technical information on genetic disorders; Online Mendelian Inheritance in Man site, hosted by Johns Hopkins University.

Genetics in Primary Care Institute (AAP)
The goal of this site is to increase collaboration in the care of children with known or suspected genetic disorders. Includes health supervision guidelines and other useful resources; a collaboration among the Health Resources & Services Administration, the Maternal and Child Health Bureau, and the American Academy of Pediatrics.

For Parents and Patients

Beta-Ketothiolase Deficiency - Information for Parents (STAR-G)
A fact sheet, written by a genetic counselor and reviewed by metabolic and genetic specialists, for families who have received an initial diagnosis of this newborn disorder; Screening, Technology and Research in Genetics.

Beta-Ketothiolase Deficiency (Genetics Home Reference)
Excellent, detailed review of condition for patients and families; U.S. National Library of Medicine.

Organic Acidemia Association (OAA)
A nonprofit organization that provides information, newsletters, calendars of events, connections with other parents, a listserv, a discussion board, and nutrition and recipe ideas.


Genetics-related clinical services throughout the world can be found through Genetics Clinic Directory (GeneTests).

Newborn Screening Programs

See all Newborn Screening Programs services providers (3) in our database.

Pediatric Genetics

See all Pediatric Genetics services providers (5) in our database.

For other services related to this condition, browse our Services categories or search our database.

Helpful Articles

PubMed search for newborn screening and beta-ketothiolase deficiency, last 10 years.

Pasquali M, Monsen G, Richardson L, Alston M, Longo N.
Biochemical findings in common inborn errors of metabolism.
Am J Med Genet C Semin Med Genet. 2006;142C(2):64-76. PubMed abstract

Korman SH.
Inborn errors of isoleucine degradation: a review.
Mol Genet Metab. 2006;89(4):289-99. PubMed abstract


Reviewing Authors: Kimberly Hart, MS, LCGC - 6/2012
Nicola Longo, MD, PhD - 3/2007
Compiled and edited by: Alfred Romeo, RN, PhD - 3/2007
Content Last Updated: 6/2012