Journal article
Disturbed sphingolipid metabolism with elevated 1-deoxysphingolipids in glycogen storage disease type I - A link to metabolic control.
- Hornemann T Institute of Clinical Chemistry, University Hospital Zurich, Zurich, Switzerland.
- Alecu I Institute of Clinical Chemistry, University Hospital Zurich, Zurich, Switzerland. Electronic address: rina.alecu@gmail.com.
- Hagenbuch N Institute of Biostatistics, University of Zurich, Zurich, Switzerland.
- Zhakupova A Institute of Clinical Chemistry, University Hospital Zurich, Zurich, Switzerland.
- Cremonesi A Institute of Clinical Chemistry, University Children's Hospital, Zurich, Switzerland.
- Gautschi M Department of Pediatrics and Institute of Clinical Chemistry, University Hospital Bern, Inselspital, Bern, Switzerland.
- Jung HH Department of Neurology, University Hospital Zurich, Zurich, Switzerland.
- Meienberg F Department of Endocrinology, Diabetes and Metabolism, University Hospital, Basel, Switzerland.
- Bilz S Division of Endocrinology, Kantonsspital St. Gallen, St. Gallen, Switzerland.
- Christ E Department of Diabetes, Endocrinology, Nutritional medicine and Metabolism, University Hospital Bern, Inselspital, Bern, Switzerland.
- Baumgartner MR Division of Metabolism and Children's Research Center (CRC), University Children's Hospital, Zurich, Switzerland.; Radiz - Rare Disease Initiative Zurich, Clinical Research Priority Program for Rare Diseases, University of Zurich, Switzerland.
- Hochuli M Division of Endocrinology, Diabetes, and Clinical Nutrition, University Hospital Zurich, Zurich, Switzerland; Radiz - Rare Disease Initiative Zurich, Clinical Research Priority Program for Rare Diseases, University of Zurich, Switzerland. Electronic address: michel.hochuli@usz.ch.
- 2018-07-25
Published in:
- Molecular genetics and metabolism. - 2018
Deoxysphingolipids
GSD
Glucose
Glycogen storage disease
Lipids
Metabolism
Adolescent
Adult
Alanine
Female
Glucose
Glycogen Storage Disease Type I
Humans
Lipid Metabolism
Male
Serine
Serine C-Palmitoyltransferase
Sphingolipids
Young Adult
English
BACKGROUND
1-Deoxysphingolipids (1-deoxySLs) are atypical sphingolipids. They are formed during sphingolipid de novo synthesis by the enzyme serine palmitoyltransferase, due to the alternate use of alanine over its canonical substrate serine. Pathologically elevated 1-deoxySL are involved in several neurological and metabolic disorders. The objective of this study was to investigate the role of 1-deoxySL in glycogen storage disease type I (GSDI).
METHODS
In this prospective, longitudinal observational study (median follow-up 1.8y), the plasma 1-deoxySL profile was analyzed in 15 adult GSDI patients (12 GSDIa, 3 GSDIb), and 31 healthy controls, along with standard parameters for monitoring GSDI.
RESULTS
1-Deoxysphinganine (1-deoxySA) concentrations were elevated in GSDI compared to controls (191 ± 129 vs 35 ± 14 nmol/l, p < 0.0001). Concordant with the mechanism of 1-deoxySL synthesis, plasma alanine was higher (625 ± 182 vs 398 ± 90 μmol/l, p < 0.0001), while serine was lower in GSDI than in controls (88 ± 22 vs 110 ± 18 μmol/l. p < 0.001). Accordingly, serine, alanine and triglycerides were determinants of 1-deoxySA in the longitudinal analysis of GSDIa. 1-deoxySA concentrations correlated with the occurrence of low blood glucose (area under the curve below 4 mmol/l) in continuous glucose monitoring. The 1-deoxySL profile in GSDIb was distinct from GSDIa, with a different ratio of saturated to unsaturated 1-deoxySL.
CONCLUSION
In addition to the known abnormalities of lipoproteins, GSDI patients also have a disturbed sphingolipid metabolism with elevated plasma 1-deoxySL concentrations. 1-DeoxySA relates to the occurrence of low blood glucose, and may constitute a potential new biomarker for assessing metabolic control. GSDIa and Ib have distinct 1-deoxySL profiles indicating that both GSD subtypes have diverse phenotypes regarding lipid metabolism.
1-Deoxysphingolipids (1-deoxySLs) are atypical sphingolipids. They are formed during sphingolipid de novo synthesis by the enzyme serine palmitoyltransferase, due to the alternate use of alanine over its canonical substrate serine. Pathologically elevated 1-deoxySL are involved in several neurological and metabolic disorders. The objective of this study was to investigate the role of 1-deoxySL in glycogen storage disease type I (GSDI).
METHODS
In this prospective, longitudinal observational study (median follow-up 1.8y), the plasma 1-deoxySL profile was analyzed in 15 adult GSDI patients (12 GSDIa, 3 GSDIb), and 31 healthy controls, along with standard parameters for monitoring GSDI.
RESULTS
1-Deoxysphinganine (1-deoxySA) concentrations were elevated in GSDI compared to controls (191 ± 129 vs 35 ± 14 nmol/l, p < 0.0001). Concordant with the mechanism of 1-deoxySL synthesis, plasma alanine was higher (625 ± 182 vs 398 ± 90 μmol/l, p < 0.0001), while serine was lower in GSDI than in controls (88 ± 22 vs 110 ± 18 μmol/l. p < 0.001). Accordingly, serine, alanine and triglycerides were determinants of 1-deoxySA in the longitudinal analysis of GSDIa. 1-deoxySA concentrations correlated with the occurrence of low blood glucose (area under the curve below 4 mmol/l) in continuous glucose monitoring. The 1-deoxySL profile in GSDIb was distinct from GSDIa, with a different ratio of saturated to unsaturated 1-deoxySL.
CONCLUSION
In addition to the known abnormalities of lipoproteins, GSDI patients also have a disturbed sphingolipid metabolism with elevated plasma 1-deoxySL concentrations. 1-DeoxySA relates to the occurrence of low blood glucose, and may constitute a potential new biomarker for assessing metabolic control. GSDIa and Ib have distinct 1-deoxySL profiles indicating that both GSD subtypes have diverse phenotypes regarding lipid metabolism.
- Language
-
- English
- Open access status
- closed
- Identifiers
-
- DOI 10.1016/j.ymgme.2018.07.003
- PMID 30037504
- Persistent URL
- https://sonar.ch/global/documents/201385
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