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3-Hydroxy-3-methylglutaryl-coenzyme A lyase deficiency: Clinical presentation and outcome in a series of 37 patients
SC. Grünert, SM. Schlatter, RN. Schmitt, C. Gemperle-Britschgi, L. Mrázová, MC. Balcı, F. Bischof, M. Çoker, AM. Das, M. Demirkol, M. de Vries, G. Gökçay, J. Häberle, SK. Uçar, AS. Lotz-Havla, T. Lücke, D. Roland, F. Rutsch, R. Santer, A....
Language English Country United States
Document type Journal Article, Multicenter Study
- MeSH
- Acetyl-CoA C-Acetyltransferase deficiency MeSH
- Child MeSH
- Adult MeSH
- Genetic Association Studies MeSH
- Patient Outcome Assessment MeSH
- Ketone Bodies metabolism MeSH
- Infant MeSH
- Leucine metabolism MeSH
- Humans MeSH
- Oxo-Acid-Lyases genetics MeSH
- Fatty Acids metabolism MeSH
- Adolescent MeSH
- Young Adult MeSH
- Mutation MeSH
- Child, Preschool MeSH
- Amino Acid Metabolism, Inborn Errors * complications diagnosis diet therapy physiopathology MeSH
- Check Tag
- Child MeSH
- Adult MeSH
- Infant MeSH
- Humans MeSH
- Adolescent MeSH
- Young Adult MeSH
- Male MeSH
- Child, Preschool MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Multicenter Study MeSH
- Geographicals
- Belgium MeSH
- Germany MeSH
- Netherlands MeSH
- Switzerland MeSH
- Turkey MeSH
3-Hydroxy-3-methylglutaryl-coenzyme A lyase deficiency (HMGCLD) is a rare inborn error of ketone body synthesis and leucine degradation, caused by mutations in the HMGCL gene. In order to obtain a comprehensive view on this disease, we have collected clinical and biochemical data as well as information on HMGCL mutations of 37 patients (35 families) from metabolic centers in Belgium, Germany, The Netherlands, Switzerland, and Turkey. All patients were symptomatic at some stage with 94% presenting with an acute metabolic decompensation. In 50% of the patients, the disorder manifested neonatally, mostly within the first days of life. Only 8% of patients presented after one year of age. Six patients died prior to data collection. Long-term neurological complications were common. Half of the patients had a normal cognitive development while the remainder showed psychomotor deficits. We identified seven novel HMGCL mutations. In agreement with previous reports, no clear genotype-phenotype correlation could be found. This is the largest cohort of HMGCLD patients reported so far, demonstrating that HMGCLD is a potentially life-threatening disease with variable clinical outcome. Our findings suggest that the clinical course of HMGCLD cannot be predicted accurately from HMGCL genotype. The overall outcome in HMGCLD appears limited, thus rendering early diagnosis and strict avoidance of metabolic crises important.
Département de Biochimie Université de Montréal Montréal Québec Canada
Department of General Pediatrics Münster University Children's Hospital Münster Germany
Department of Neurology University of Tübingen Germany
Department of Neuropediatrics University Children's Hospital Ruhr University Bochum Bochum Germany
Department of Pediatrics Hannover Medical School Hannover Germany
Department of Pediatrics University Medical Center Hamburg Eppendorf Hamburg Germany
Inborn Errors of Metabolism Unit Institute of Pathology and Genetics Charleroi Gosselies Belgium
References provided by Crossref.org
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- $a Grünert, Sarah Catharina $u Department of General Pediatrics, Adolescent Medicine and Neonatology, Medical Center - University of Freiburg, Faculty of Medicine, Freiburg, Germany.
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