Home > Newborn Disorders > Beta-Ketothiolase deficiency
Beta-Ketothiolase deficiency
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
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 with a decreased ability to generate energy. Patients typically present with metabolic acidosis induced by fasting, infection, fever or vomiting.Prevalence
rare [Beta-Ketothiolase deficiency info for professionals (STAR-G)]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; and
- hypoglycemia or occasionally hyperglycemia.
If not treated promptly, patients may experience:
- acute metabolic acidosis,
- failure to thrive,
- intellectual disability, and
- death.
Follow-up on positive screening test
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 in dubious cases.Primary care management
Upon notification of the + screen
- Contact the family and evaluate the infant for poor feeding, vomiting, lethargy;
- Provide emergency treatment/referral for symptoms of hypoglycemia, ketonuria, or acidosis;
- To confirm the diagnosis, work with the following service(s): Utah Newborn Screening Program, (801-584-8256); See also Services below;
- For evaluation and ongoing collaborative management, consult the following service(s): Medical Genetics, (801-231-3599); See also Services below;
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 the 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.Resources
Information & Support
For Professionals
Beta-Ketothiolase deficiency info for professionals (STAR-G)
From the Screening, Technology and Research in Genetics (STAR-G) program, 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 Elevated C5-OH Acylcarnitine (ACMG)
(
400 KB)
Developed by the American College of Medical Genetics, includes recommended responses to positive newborn screening test results,
diagnostic evaluation, clinical expectations, and sources of additional information.
ACT Sheets and Confirmatory Algorithms (ACMG)
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.
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 the literature, including clinical features and genetics, 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 and Patients
Beta-Ketothiolase deficiency info for parents (STAR-G)
From the Screening, Technology and Research in Genetics (STAR-G) program, 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, UT 84114
Phone: 801-584-8256
Fax: 801-536-0966
http://health.utah.gov/newbornscreening
Pediatric Medical Genetics
See all Pediatric Medical 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.
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
| Reviewing Author: | Nicola Longo MD, PhD, 3/2007 |
| Compiled and edited by: | Alfred Romeo RN, PhD, 3/2007 |
| Content Last Updated: | 9/2010 |