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2-methylacetoacetyl-coenzyme A thiolase (beta-ketothiolase) deficiency: one disease - two pathways
Sarah Catharina Grünert
Department of Pediatrics, Adolescent Medicine and Neonatology, Medical Center - University of Freiburg, Faculty of Medicine, Freiburg
Corresponding Author
ORCiD: https://orcid.org/0000-0001-5986-0468
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This work is licensed under a CC BY 4.0 License. Read Full License
Background: 2-methylacetoacetyl-coenzyme A thiolase deficiency (MATD; deficiency of mitochondrial acetoacetyl-coenzyme A thiolase T2/ “beta-ketothiolase”) is an autosomal recessive disorder of ketone body utilization and isoleucine degradation due to mutations in ACAT1.
Methods: We performed a systematic literature search for all available clinical descriptions of patients with MATD. 244 patients were identified and included in this analysis. Clinical course and biochemical data are presented and discussed.
Results: For 89.6 % of patients at least one acute metabolic decompensation was reported. Age at first symptoms ranged from 2 days to 8 years (median 12 months). More than 82% of patients presented in the first two years of life, while manifestation in the neonatal period was the exception (3.4%). 77.0% (157 of 204 patients) of patients showed normal psychomotor development without neurologic abnormalities.
Conclusion: This comprehensive data analysis provides a systematic overview on all cases with MATD identified in the literature. It demonstrates that MATD is a rather benign disorder with often favourable outcome, when compared with many other organic acidurias.
Keywords
Ketolysis, beta-ketothiolase. organic aciduria, isoleucine, ketone body, metabolic acidosis, metabolic decompensation, ACAT1, inborn error of metabolism
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CURRENT STATUS: Under Review
Version 1
Posted 23 Dec, 2019
No community comments so far
Editorial decision: Major revision
On 10 Feb, 2020
Review #2 received
Received 08 Feb, 2020
Reviewer #2 agreed
On 23 Jan, 2020
Review #1 received
Received 23 Jan, 2020
Reviewer #1 agreed
On 30 Dec, 2019
Reviewers invited
Invitations sent on 28 Dec, 2019
Editor assigned
On 19 Dec, 2019
First submitted
On 18 Dec, 2019
Submission checks complete
On 18 Dec, 2019
Editor invited
On 18 Dec, 2019
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Subject Areas
Internal Medicine
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This preprint is under consideration at Orphanet Journal of Rare Disease. A preprint is a preliminary version of a manuscript that has not completed peer review at a journal. Research Square does not conduct peer review prior to posting preprints. The posting of a preprint on this server should not be interpreted as an endorsement of its validity or suitability for dissemination as established information or for guiding clinical practice.
Learn more about In Review
Research
2-methylacetoacetyl-coenzyme A thiolase (beta-ketothiolase) deficiency: one disease - two pathways
Sarah Catharina Grünert
Department of Pediatrics, Adolescent Medicine and Neonatology, Medical Center - University of Freiburg, Faculty of Medicine, Freiburg
Corresponding Author
ORCiD: https://orcid.org/0000-0001-5986-0468
Badges
Prescreen
This manuscript passed our Prescreen assessment
Complete author information
Appropriate declaration statements
Potential risks to human health
Prescreen
Peer Review Timeline
CURRENT STATUS: Under Review
Version 1
Posted 23 Dec, 2019
No community comments so far
Editorial decision: Major revision
On 10 Feb, 2020
Review #2 received
Received 08 Feb, 2020
Reviewer #2 agreed
On 23 Jan, 2020
Review #1 received
Received 23 Jan, 2020
Reviewer #1 agreed
On 30 Dec, 2019
Reviewers invited
Invitations sent on 28 Dec, 2019
Editor assigned
On 19 Dec, 2019
First submitted
On 18 Dec, 2019
Submission checks complete
On 18 Dec, 2019
Editor invited
On 18 Dec, 2019
Metrics
Comments: 0
PDF Downloads: ...
HTML Views: ...
Subject Areas
Internal Medicine
License:
This work is licensed under a CC BY 4.0 License. Read Full License
Background: 2-methylacetoacetyl-coenzyme A thiolase deficiency (MATD; deficiency of mitochondrial acetoacetyl-coenzyme A thiolase T2/ “beta-ketothiolase”) is an autosomal recessive disorder of ketone body utilization and isoleucine degradation due to mutations in ACAT1.
Methods: We performed a systematic literature search for all available clinical descriptions of patients with MATD. 244 patients were identified and included in this analysis. Clinical course and biochemical data are presented and discussed.
Results: For 89.6 % of patients at least one acute metabolic decompensation was reported. Age at first symptoms ranged from 2 days to 8 years (median 12 months). More than 82% of patients presented in the first two years of life, while manifestation in the neonatal period was the exception (3.4%). 77.0% (157 of 204 patients) of patients showed normal psychomotor development without neurologic abnormalities.
Conclusion: This comprehensive data analysis provides a systematic overview on all cases with MATD identified in the literature. It demonstrates that MATD is a rather benign disorder with often favourable outcome, when compared with many other organic acidurias.
Figure 1
Figure 2
Figure 3
Figure 4