Non-invasive test using palmitate in patients with suspected fatty acid oxidation defects: disease-specific acylcarnitine patterns can help to establish the diagnosis
Abstract Background The aim of the present study was to establish a non-invasive, fast and robust enzymatic assay to confirm fatty acid oxidation defects (FAOD) in humans following informative newborn-screening or for selective screening of patients suspected to suffer from FAOD. Material/methods Th...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2017-12-01
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| Series: | Orphanet Journal of Rare Diseases |
| Subjects: | |
| Online Access: | http://link.springer.com/article/10.1186/s13023-017-0737-7 |
| _version_ | 1819274269610213376 |
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| author | Nils Janzen Alejandro D. Hofmann Gunnar Schmidt Anibh M. Das Sabine Illsinger |
| author_facet | Nils Janzen Alejandro D. Hofmann Gunnar Schmidt Anibh M. Das Sabine Illsinger |
| author_sort | Nils Janzen |
| collection | DOAJ |
| description | Abstract Background The aim of the present study was to establish a non-invasive, fast and robust enzymatic assay to confirm fatty acid oxidation defects (FAOD) in humans following informative newborn-screening or for selective screening of patients suspected to suffer from FAOD. Material/methods The reliability of this method was tested in whole blood from FAOD patients with specific enzymatic defects. Whole blood samples were assayed in 30 medium chain- (MCADD, age 0 to 17 years), 6 very long chain- (VLCADD, age 0 to 4 years), 6 long chain hydroxy- (LCHAD, age 1 to 6 years), 3 short chain- (SCADD, age 10 to 13 years) acyl-CoA-dehydrogenase- and 2 primary carnitine transporter deficiencies (CTD, age 3 to 5 years). Additionally, 26 healthy children (age 0 to 17 years) served as controls. Whole blood samples were incubated with stable end-labeled palmitate; labeled acylcarnitines were analyzed by tandem mass spectrometry and compared with controls and between patient groups (Mann-Whitney Rank Sum Test). Concentrations of specific labeled acylcarnitine metabolites were compared between particular underlying MCADD- (ANOVA), VLCADD- and LCHADD- genetic variants (descriptive data analysis). Results 11 different acylcarnitines were analyzed. MCADD- (C8-, C10-carnitine, C8/C10- and C8/C4-carnitine), VLCADD- (C12-, C14:1-, C14:2-carnitine, C14:1/C12- and C14:2/C12-carnitine), LCHADD (C16-OH-carnitine) as well as CTD- deficiency (sum of all acylcarnitines) samples could be clearly identified and separated from control values as well as other FAOD, whereas the sum of all acylcarnitines was not conclusive between FAOD samples. Furthermore, C4- (SCADD), C14- (VLCADD) and C14-OH-carnitines (LCHADD) were discriminating between the FAOD groups. Metabolic parameters did not differ significantly between underlying MCADD variants; similar results could be observed for VLCADD- and LCHADD- variants. Conclusion This functional method in whole blood samples is relatively simple, non-invasive and little time consuming. It allows to identify MCADD-, VLCADD-, LCHADD- and carnitine transporter deficiencies. The genetic phenotypes of one enzyme defect did not result in differing acylcarnitine patterns in MCADD, VLCADD or LCHADD in vitro. |
| first_indexed | 2024-12-23T23:05:45Z |
| format | Article |
| id | doaj.art-02d88aae866741f2854853d1f98bcedf |
| institution | Directory Open Access Journal |
| issn | 1750-1172 |
| language | English |
| last_indexed | 2024-12-23T23:05:45Z |
| publishDate | 2017-12-01 |
| publisher | BMC |
| record_format | Article |
| series | Orphanet Journal of Rare Diseases |
| spelling | doaj.art-02d88aae866741f2854853d1f98bcedf2022-12-21T17:26:48ZengBMCOrphanet Journal of Rare Diseases1750-11722017-12-011211810.1186/s13023-017-0737-7Non-invasive test using palmitate in patients with suspected fatty acid oxidation defects: disease-specific acylcarnitine patterns can help to establish the diagnosisNils Janzen0Alejandro D. Hofmann1Gunnar Schmidt2Anibh M. Das3Sabine Illsinger4Screening Laboratory HannoverCenter of Pediatric Surgery, Hannover Medical School and Bult Children’s HospitalInstitute of Human Genetics, Hannover Medical SchoolClinic for Pediatric Kidney-, Liver- and Metabolic Diseases, Hannover Medical SchoolClinic for Pediatric Kidney-, Liver- and Metabolic Diseases, Hannover Medical SchoolAbstract Background The aim of the present study was to establish a non-invasive, fast and robust enzymatic assay to confirm fatty acid oxidation defects (FAOD) in humans following informative newborn-screening or for selective screening of patients suspected to suffer from FAOD. Material/methods The reliability of this method was tested in whole blood from FAOD patients with specific enzymatic defects. Whole blood samples were assayed in 30 medium chain- (MCADD, age 0 to 17 years), 6 very long chain- (VLCADD, age 0 to 4 years), 6 long chain hydroxy- (LCHAD, age 1 to 6 years), 3 short chain- (SCADD, age 10 to 13 years) acyl-CoA-dehydrogenase- and 2 primary carnitine transporter deficiencies (CTD, age 3 to 5 years). Additionally, 26 healthy children (age 0 to 17 years) served as controls. Whole blood samples were incubated with stable end-labeled palmitate; labeled acylcarnitines were analyzed by tandem mass spectrometry and compared with controls and between patient groups (Mann-Whitney Rank Sum Test). Concentrations of specific labeled acylcarnitine metabolites were compared between particular underlying MCADD- (ANOVA), VLCADD- and LCHADD- genetic variants (descriptive data analysis). Results 11 different acylcarnitines were analyzed. MCADD- (C8-, C10-carnitine, C8/C10- and C8/C4-carnitine), VLCADD- (C12-, C14:1-, C14:2-carnitine, C14:1/C12- and C14:2/C12-carnitine), LCHADD (C16-OH-carnitine) as well as CTD- deficiency (sum of all acylcarnitines) samples could be clearly identified and separated from control values as well as other FAOD, whereas the sum of all acylcarnitines was not conclusive between FAOD samples. Furthermore, C4- (SCADD), C14- (VLCADD) and C14-OH-carnitines (LCHADD) were discriminating between the FAOD groups. Metabolic parameters did not differ significantly between underlying MCADD variants; similar results could be observed for VLCADD- and LCHADD- variants. Conclusion This functional method in whole blood samples is relatively simple, non-invasive and little time consuming. It allows to identify MCADD-, VLCADD-, LCHADD- and carnitine transporter deficiencies. The genetic phenotypes of one enzyme defect did not result in differing acylcarnitine patterns in MCADD, VLCADD or LCHADD in vitro.http://link.springer.com/article/10.1186/s13023-017-0737-7Fatty acid oxidationTandem mass spectrometrySCADDMCADDVLCADDLCHADD |
| spellingShingle | Nils Janzen Alejandro D. Hofmann Gunnar Schmidt Anibh M. Das Sabine Illsinger Non-invasive test using palmitate in patients with suspected fatty acid oxidation defects: disease-specific acylcarnitine patterns can help to establish the diagnosis Orphanet Journal of Rare Diseases Fatty acid oxidation Tandem mass spectrometry SCADD MCADD VLCADD LCHADD |
| title | Non-invasive test using palmitate in patients with suspected fatty acid oxidation defects: disease-specific acylcarnitine patterns can help to establish the diagnosis |
| title_full | Non-invasive test using palmitate in patients with suspected fatty acid oxidation defects: disease-specific acylcarnitine patterns can help to establish the diagnosis |
| title_fullStr | Non-invasive test using palmitate in patients with suspected fatty acid oxidation defects: disease-specific acylcarnitine patterns can help to establish the diagnosis |
| title_full_unstemmed | Non-invasive test using palmitate in patients with suspected fatty acid oxidation defects: disease-specific acylcarnitine patterns can help to establish the diagnosis |
| title_short | Non-invasive test using palmitate in patients with suspected fatty acid oxidation defects: disease-specific acylcarnitine patterns can help to establish the diagnosis |
| title_sort | non invasive test using palmitate in patients with suspected fatty acid oxidation defects disease specific acylcarnitine patterns can help to establish the diagnosis |
| topic | Fatty acid oxidation Tandem mass spectrometry SCADD MCADD VLCADD LCHADD |
| url | http://link.springer.com/article/10.1186/s13023-017-0737-7 |
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