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Screening & Prevention >> Newborn Screening >> Organic Acidemias >> Beta-Ketothiolase deficiency

Beta-Ketothiolase deficiency

Disorder Category

an organic acid disorder

Screening

Finding

elevated C5-OH (acylcarnitine), elevated C5:1 (tiglycarnitine)

Tested By

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

Names

Beta-Ketothiolase deficiency

BKD

Alpha-methylacetoacetic aciduria

2-methyl-3-hydroxybutyric acidemia

Mitochondrial acetoacetyl-CoA thiolase (MAT) deficiency

3-ketothiolase deficiency

3-oxothiolase deficiency

ICD-9

270.3, Disturbances of branched-chain amino-acid metabolism

Overview

Due to absence of the enzyme mitochondrial acetoacetyl-CoA thiolase, patients are unable to break down the amino acid isoleucine and cannot utilize liver-generate ketone bodies causing a buildup of organic acids and inability to generate energy.

Prevalence

rare [Beta-Ketothiolase deficiency info for professionals, STAR-G]

Inheritance

autosomal recessive

Prenatal Testing

DNA and enzyme testing by amniocentesis or CVS.

Clinical Characteristics

With treatment, normal development can be expected despite 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, consuming too much protein, and illness.

Initial signs/symptoms may include:
  • feeding problems;
  • vomiting, possibly with hematemesis;
  • diarrhea;
  • lethargy progressing to coma; and
  • hypoglycemia.


If not treated promptly, patients may experience:
  • short stature,
  • renal failure,
  • cardiomyopathy,
  • mental retardation, and
  • death.

Follow-up on positive screening test

Quantitative plasma acylcarnitine profile, serum biotinidase assay, urine organic acids.

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;
  • Oral L-carnitine may be indicated for some affected children;
  • Bicarbonate and intravenous glucose may be indicated during metabolic crisis;
  • Monitor urine ketone levels periodically;
  • For those identified after irreversible consequences, assist in management, particularly with developmental and educational interventions.

Specialty Care Management

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

Resources

Links

For Professionals

Beta-Ketothiolase deficiency info for professionals, STAR-G
On the Screening, Technology and Research in Genetics (STAR-G) site, one of a series of Disorder Fact Sheets for Professionals; structured list of information about the condition, with links to more information.

ACT Sheet for Beta-Ketothiolase deficiency from ACMG (pdf 132kb)
Developed by the American College of Medical Genetics (ACMG), includes recommended responses to positive newborn screening test results, diagnostic evaluation, clinical expectations, and sources of additional information. See the ACMG ACT Sheets and Confirmatory Algorithms (link elsewhere on this page) for more info and sheets on other conditions.

ACMG ACT Sheets and Confirmatory Algorithms
The American College of Medical Genetics (ACMG) has developed ACTion (ACT) Sheets and algorithms for responding to positive newborn screening test results. This page contains a table with links to all of the ACT Sheets and related algorithms.

Beta-Ketothiolase deficiency, OMIM
Extensive review of the literature, including clinical features and gene therapy, from the Online Mendelian Inheritance in Man site, hosted by Johns Hopkins University, providing technical information for providers on genetic disorders, links to MEDLINE, and links to other scientific information and sites.

For Parents

Beta-Ketothiolase deficiency info for parents, STAR-G
From the Screening, Technology and Research in Genetics (STAR-G) site, providing information for parents about beta-ketothiolase deficiency and links to other sites including parent support groups.

Beta-Ketothiolase deficiency, Genetics Home Reference
Excellent, detailed review aimed at patients and families from the National Library of Medicine's Genetics Home Reference site.

Organic Acidemia Association (OAA)
A non-profit organization that provides information for parents and providers; newsletters; event information; connections with other parents; a listserv; a discussion board; information about nutrition and recipes; translation of their web pages into five other languages; hosting of the Propionic Acidemia Research Network and other research funds; and links to other sites.

Services

Newborn Screening Programs

Utah Newborn Screening Program, more info...
44 Mario Capecchi Drive
Salt Lake City, UT84114
Phone: 801-584-8256
Fax: 801-536-0966
http://health.utah.gov/newbornscreening

Pediatric Genetics

Metabolic Clinic, more info...
100 Mario Capecchi Drive
Salt Lake City, UT84113
Phone: 801-585-2457
Fax: 585-7252
http://www.ped.med.utah.edu/divisions/divisions.htm

See all Pediatric Genetics services providers (3) in our database.

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

Helpful Articles

PubMed search for review articles on beta-ketothiolase deficiency in the last 5 years.

Authors

Reviewing Author: Nicola Longo MD, PhD, 3/2007
Compiled and edited by: Alfred Romeo RN, PhD, 3/2007
Content Last Updated: 3/2008
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