Fasting and non‐fasting plasma levels of monomethyl branched chain fatty acids: Implications for maple syrup urine disease
Abstract The branched‐chain amino acids (BCAA) leucine, valine, and isoleucine provide precursors for monomethyl branched‐chain fatty acids (BCFA). Established reference ranges for BCFAs are lacking. In maple syrup urine disease (MSUD), a rare inborn error of BCAA metabolism, the endogen production...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2023-09-01
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| Series: | JIMD Reports |
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| Online Access: | https://doi.org/10.1002/jmd2.12380 |
| _version_ | 1827822339381788672 |
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| author | Trine Tangeraas Erle Kristensen Lars Mørkrid Elisabeth Elind Yngve Thomas Bliksrud Lars Eide |
| author_facet | Trine Tangeraas Erle Kristensen Lars Mørkrid Elisabeth Elind Yngve Thomas Bliksrud Lars Eide |
| author_sort | Trine Tangeraas |
| collection | DOAJ |
| description | Abstract The branched‐chain amino acids (BCAA) leucine, valine, and isoleucine provide precursors for monomethyl branched‐chain fatty acids (BCFA). Established reference ranges for BCFAs are lacking. In maple syrup urine disease (MSUD), a rare inborn error of BCAA metabolism, the endogen production is impaired and MSUD patients are treated with a low protein (low BCAA) diet. The protein restriction may affect the dietary intake of BCFA, depending on the dietary choices made. Patients with MSUD are prescribed a more or less protein‐restricted diet depending on the severity of the disease. The combination of a protein‐restricted diet and subsequent impaired endogenous synthesis may render MSUD patients sensitive to BCFA deficiency, with yet unknown implications. To investigate the possibility of lower circulatory BCFA levels in MSUD that favors dietary BCFA supplementation, we first established fasting‐state reference ranges for selected BCFAs and saturated/unsaturated fatty acids in plasma. Then, the effect of fasting on BCFA levels was evaluated by comparing the distribution in a fasting versus a non‐fasting cohort. To test the hypothesis that BCFA deficiency could contribute to MSUD pathophysiology, we recruited patients with intermittent, intermediate, and classical form of MSUD and analyzed the corresponding BCFA z‐scores. None of the BCFA species had |z‐scores| > 2 relative to the reference range. Our findings do not support the requirement of BCFA supplementation in MSUD patients. The origin of BCFAs is discussed. Impaired capacity to synthesize BCFA do not manifest as reduced plasma levels in MSUD, suggesting that endogenous synthesis is dispensable for plasma levels. |
| first_indexed | 2024-03-12T01:56:38Z |
| format | Article |
| id | doaj.art-e6789926733e432db18bbd9524690732 |
| institution | Directory Open Access Journal |
| issn | 2192-8312 |
| language | English |
| last_indexed | 2024-03-12T01:56:38Z |
| publishDate | 2023-09-01 |
| publisher | Wiley |
| record_format | Article |
| series | JIMD Reports |
| spelling | doaj.art-e6789926733e432db18bbd95246907322023-09-08T04:48:16ZengWileyJIMD Reports2192-83122023-09-0164536036610.1002/jmd2.12380Fasting and non‐fasting plasma levels of monomethyl branched chain fatty acids: Implications for maple syrup urine diseaseTrine Tangeraas0Erle Kristensen1Lars Mørkrid2Elisabeth Elind3Yngve Thomas Bliksrud4Lars Eide5Department of Newborn Screening Oslo University Hospital Oslo NorwayDepartment of Medical Biochemistry Oslo University Hospital Oslo NorwayDepartment of Medical Biochemistry Oslo University Hospital Oslo NorwayDepartment of Newborn Screening Oslo University Hospital Oslo NorwayDepartment of Medical Biochemistry Oslo University Hospital Oslo NorwayDepartment of Medical Biochemistry Oslo University Hospital Oslo NorwayAbstract The branched‐chain amino acids (BCAA) leucine, valine, and isoleucine provide precursors for monomethyl branched‐chain fatty acids (BCFA). Established reference ranges for BCFAs are lacking. In maple syrup urine disease (MSUD), a rare inborn error of BCAA metabolism, the endogen production is impaired and MSUD patients are treated with a low protein (low BCAA) diet. The protein restriction may affect the dietary intake of BCFA, depending on the dietary choices made. Patients with MSUD are prescribed a more or less protein‐restricted diet depending on the severity of the disease. The combination of a protein‐restricted diet and subsequent impaired endogenous synthesis may render MSUD patients sensitive to BCFA deficiency, with yet unknown implications. To investigate the possibility of lower circulatory BCFA levels in MSUD that favors dietary BCFA supplementation, we first established fasting‐state reference ranges for selected BCFAs and saturated/unsaturated fatty acids in plasma. Then, the effect of fasting on BCFA levels was evaluated by comparing the distribution in a fasting versus a non‐fasting cohort. To test the hypothesis that BCFA deficiency could contribute to MSUD pathophysiology, we recruited patients with intermittent, intermediate, and classical form of MSUD and analyzed the corresponding BCFA z‐scores. None of the BCFA species had |z‐scores| > 2 relative to the reference range. Our findings do not support the requirement of BCFA supplementation in MSUD patients. The origin of BCFAs is discussed. Impaired capacity to synthesize BCFA do not manifest as reduced plasma levels in MSUD, suggesting that endogenous synthesis is dispensable for plasma levels.https://doi.org/10.1002/jmd2.12380fastingisoleucineleucinemonomethyl branched‐chain fatty acidsMSUDvaline |
| spellingShingle | Trine Tangeraas Erle Kristensen Lars Mørkrid Elisabeth Elind Yngve Thomas Bliksrud Lars Eide Fasting and non‐fasting plasma levels of monomethyl branched chain fatty acids: Implications for maple syrup urine disease JIMD Reports fasting isoleucine leucine monomethyl branched‐chain fatty acids MSUD valine |
| title | Fasting and non‐fasting plasma levels of monomethyl branched chain fatty acids: Implications for maple syrup urine disease |
| title_full | Fasting and non‐fasting plasma levels of monomethyl branched chain fatty acids: Implications for maple syrup urine disease |
| title_fullStr | Fasting and non‐fasting plasma levels of monomethyl branched chain fatty acids: Implications for maple syrup urine disease |
| title_full_unstemmed | Fasting and non‐fasting plasma levels of monomethyl branched chain fatty acids: Implications for maple syrup urine disease |
| title_short | Fasting and non‐fasting plasma levels of monomethyl branched chain fatty acids: Implications for maple syrup urine disease |
| title_sort | fasting and non fasting plasma levels of monomethyl branched chain fatty acids implications for maple syrup urine disease |
| topic | fasting isoleucine leucine monomethyl branched‐chain fatty acids MSUD valine |
| url | https://doi.org/10.1002/jmd2.12380 |
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