Beta-Ketothiolase Deficiency

Other Names

Alpha-methylacetoacetic aciduria


Mitochondrial acetoacetyl-CoA thiolase (MAT) deficiency

3-ketothiolase deficiency

3-oxothiolase deficiency

2-methyl-3-hydroxybutyric acidemia

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 the absence of the enzyme mitochondrial acetoacetyl-CoA thiolase, patients are unable to break down the amino acid isoleucine and to utilize ketone bodies. This results in a buildup of organic acids (ketones) 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 is 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 ranges from 3 days to 4 years with the mean age at presentation of 15 months. Symptoms are usually triggered by fasting and illness.

Initial signs/symptoms may include:
  • Feeding problems
  • Vomiting
  • 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. Patients with milder variants can be missed by newborn screening or have elevation of other acylcarnitine species.

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 before bedtime 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 need to be utilized 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 (OMIM)
Information about clinical features, diagnosis, management, and molecular and population genetics; Online Mendelian Inheritance in Man, authored and edited at the McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine

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 (MedlinePlus)
Information for families that includes description, frequency, causes, inheritance, other names, and additional resources; from the National Library of Medicine.

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

Resources for Beta-Ketothiolase Deficiency (Disease InfoSearch)
Compilation of information, articles, and links to support; from Genetic Alliance.


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.

Services for Patients & Families in Montana (MT)

Genetics clinic services throughout the US can be found through the Genetics Clinic Services Search Engine (ACMG)

For services not listed above, browse our Services categories or search our database.

* number of provider listings may vary by how states categorize services, whether providers are listed by organization or individual, how services are organized in the state, and other factors; Nationwide (NW) providers are generally limited to web-based services, provider locator services, and organizations that serve children from across the nation.

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

Authors & Reviewers

Initial publication: March 2007; last update/revision: May 2019
Current Authors and Reviewers:
Author: Nicola Longo, MD, Ph.D.
Authoring history
2012: revision: Kimberly Hart, MS, LCGCA
2007: first version: Nicola Longo, MD, Ph.D.A
AAuthor; CAContributing Author; SASenior Author; RReviewer