Very long‐chain acyl‐CoA dehydrogenase deficiency in a Swedish cohort: Clinical symptoms, newborn screening, enzyme activity, and genetics
Abstract Very long‐chain acyl‐CoA dehydrogenase deficiency (VLCADD) is a recessive disorder of fatty acid beta‐oxidation with variable phenotype. Patients may present during the neonatal period with lethal multi‐organ failure or during adulthood with a myopathic phenotype. VLCADD is included in the...
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| Format: | Article |
| Language: | English |
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Wiley
2022-03-01
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| Series: | JIMD Reports |
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| Online Access: | https://doi.org/10.1002/jmd2.12268 |
| _version_ | 1818393860257087488 |
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| author | David Olsson Michela Barbaro Charlotte Haglind Maria Halldin Svetlana Lajic Sara Tucci Rolf H. Zetterström Anna Nordenström |
| author_facet | David Olsson Michela Barbaro Charlotte Haglind Maria Halldin Svetlana Lajic Sara Tucci Rolf H. Zetterström Anna Nordenström |
| author_sort | David Olsson |
| collection | DOAJ |
| description | Abstract Very long‐chain acyl‐CoA dehydrogenase deficiency (VLCADD) is a recessive disorder of fatty acid beta‐oxidation with variable phenotype. Patients may present during the neonatal period with lethal multi‐organ failure or during adulthood with a myopathic phenotype. VLCADD is included in the Swedish newborn screening (NBS) program since 2010. The study describes the phenotype and biochemical findings in relation to the genotype, enzyme activity, and screening data in a Swedish cohort of pediatric patients with VLCADD. A total of 22 patients (20 diagnosed via NBS between 2010 and 2019, two diagnosed pre NBS) were included. Parameters analyzed were enzyme activity (palmitoyl CoA oxidation rate); ACADVL genotype; NBS results including Collaborative Laboratory Integrated Reports (CLIR) score; biochemical findings; treatment; clinical outcome. A clinical severity score (CSS) was compiled using treatment interventions and clinical symptoms. A possible correlation between CSS and VLCAD residual enzyme activity and NBS CLIR score was analyzed. The most common ACADVL variant (c.848T>C) was identified in 24/44 alleles. Five novel variants were detected. Clinical manifestations varied from asymptomatic to severe. There was a correlation between CSS, residual enzyme activity, and CLIR scores. Most patients diagnosed via NBS had less severe disease compared to those clinically diagnosed. In conclusion, the identified correlation between the NBS CLIR score, residual enzyme activity, and clinical outcome suggests that information available neonatally may aid in treatment decisions. |
| first_indexed | 2024-12-14T05:52:01Z |
| format | Article |
| id | doaj.art-8328a7b424524de6862a3d3efb445668 |
| institution | Directory Open Access Journal |
| issn | 2192-8312 |
| language | English |
| last_indexed | 2024-12-14T05:52:01Z |
| publishDate | 2022-03-01 |
| publisher | Wiley |
| record_format | Article |
| series | JIMD Reports |
| spelling | doaj.art-8328a7b424524de6862a3d3efb4456682022-12-21T23:14:41ZengWileyJIMD Reports2192-83122022-03-0163218119010.1002/jmd2.12268Very long‐chain acyl‐CoA dehydrogenase deficiency in a Swedish cohort: Clinical symptoms, newborn screening, enzyme activity, and geneticsDavid Olsson0Michela Barbaro1Charlotte Haglind2Maria Halldin3Svetlana Lajic4Sara Tucci5Rolf H. Zetterström6Anna Nordenström7Department of Women's and Children's Health, Unit for Pediatric Endocrinology and Metabolic Disorders Karolinska Institutet/Karolinska University Hospital Stockholm SwedenCenter for Inherited Metabolic Diseases, CMMS Karolinska University Hospital Stockholm SwedenDepartment of Women's and Children's Health, Unit for Pediatric Endocrinology and Metabolic Disorders Karolinska Institutet/Karolinska University Hospital Stockholm SwedenDepartment of Women's and Children's Health, Unit for Pediatric Endocrinology and Metabolic Disorders Karolinska Institutet/Karolinska University Hospital Stockholm SwedenDepartment of Women's and Children's Health, Unit for Pediatric Endocrinology and Metabolic Disorders Karolinska Institutet/Karolinska University Hospital Stockholm SwedenDepartment of General Pediatrics, Adolescent Medicine and Neonatology Medical Centre‐University of Freiburg, Faculty of Medicine Freiburg GermanyCenter for Inherited Metabolic Diseases, CMMS Karolinska University Hospital Stockholm SwedenDepartment of Women's and Children's Health, Unit for Pediatric Endocrinology and Metabolic Disorders Karolinska Institutet/Karolinska University Hospital Stockholm SwedenAbstract Very long‐chain acyl‐CoA dehydrogenase deficiency (VLCADD) is a recessive disorder of fatty acid beta‐oxidation with variable phenotype. Patients may present during the neonatal period with lethal multi‐organ failure or during adulthood with a myopathic phenotype. VLCADD is included in the Swedish newborn screening (NBS) program since 2010. The study describes the phenotype and biochemical findings in relation to the genotype, enzyme activity, and screening data in a Swedish cohort of pediatric patients with VLCADD. A total of 22 patients (20 diagnosed via NBS between 2010 and 2019, two diagnosed pre NBS) were included. Parameters analyzed were enzyme activity (palmitoyl CoA oxidation rate); ACADVL genotype; NBS results including Collaborative Laboratory Integrated Reports (CLIR) score; biochemical findings; treatment; clinical outcome. A clinical severity score (CSS) was compiled using treatment interventions and clinical symptoms. A possible correlation between CSS and VLCAD residual enzyme activity and NBS CLIR score was analyzed. The most common ACADVL variant (c.848T>C) was identified in 24/44 alleles. Five novel variants were detected. Clinical manifestations varied from asymptomatic to severe. There was a correlation between CSS, residual enzyme activity, and CLIR scores. Most patients diagnosed via NBS had less severe disease compared to those clinically diagnosed. In conclusion, the identified correlation between the NBS CLIR score, residual enzyme activity, and clinical outcome suggests that information available neonatally may aid in treatment decisions.https://doi.org/10.1002/jmd2.12268clinical outcomenewborn screeningSwedenvery long‐chain acyl‐CoA dehydrogenase deficiency (VLCADD) |
| spellingShingle | David Olsson Michela Barbaro Charlotte Haglind Maria Halldin Svetlana Lajic Sara Tucci Rolf H. Zetterström Anna Nordenström Very long‐chain acyl‐CoA dehydrogenase deficiency in a Swedish cohort: Clinical symptoms, newborn screening, enzyme activity, and genetics JIMD Reports clinical outcome newborn screening Sweden very long‐chain acyl‐CoA dehydrogenase deficiency (VLCADD) |
| title | Very long‐chain acyl‐CoA dehydrogenase deficiency in a Swedish cohort: Clinical symptoms, newborn screening, enzyme activity, and genetics |
| title_full | Very long‐chain acyl‐CoA dehydrogenase deficiency in a Swedish cohort: Clinical symptoms, newborn screening, enzyme activity, and genetics |
| title_fullStr | Very long‐chain acyl‐CoA dehydrogenase deficiency in a Swedish cohort: Clinical symptoms, newborn screening, enzyme activity, and genetics |
| title_full_unstemmed | Very long‐chain acyl‐CoA dehydrogenase deficiency in a Swedish cohort: Clinical symptoms, newborn screening, enzyme activity, and genetics |
| title_short | Very long‐chain acyl‐CoA dehydrogenase deficiency in a Swedish cohort: Clinical symptoms, newborn screening, enzyme activity, and genetics |
| title_sort | very long chain acyl coa dehydrogenase deficiency in a swedish cohort clinical symptoms newborn screening enzyme activity and genetics |
| topic | clinical outcome newborn screening Sweden very long‐chain acyl‐CoA dehydrogenase deficiency (VLCADD) |
| url | https://doi.org/10.1002/jmd2.12268 |
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