1. Disturbed phospholipid metabolism in serine biosynthesis defects revealed by metabolomic profiling.
- Author
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Glinton KE, Benke PJ, Lines MA, Geraghty MT, Chakraborty P, Al-Dirbashi OY, Jiang Y, Kennedy AD, Grotewiel MS, Sutton VR, Elsea SH, and El-Hattab AW
- Subjects
- Carbohydrate Metabolism, Inborn Errors blood, Carbohydrate Metabolism, Inborn Errors diet therapy, Cell Differentiation, Child, Child, Preschool, Female, Glycine blood, Humans, Infant, Male, Metabolomics methods, Microcephaly blood, Microcephaly diet therapy, Neurons metabolism, Phosphoglycerate Dehydrogenase blood, Phosphoglycerate Dehydrogenase metabolism, Psychomotor Disorders blood, Psychomotor Disorders diet therapy, Seizures blood, Seizures diet therapy, Serine administration & dosage, Serine blood, Transaminases blood, Transaminases metabolism, Carbohydrate Metabolism, Inborn Errors metabolism, Dietary Supplements, Glycine administration & dosage, Microcephaly metabolism, Phosphatidylcholines metabolism, Phosphoglycerate Dehydrogenase deficiency, Psychomotor Disorders metabolism, Seizures metabolism, Serine biosynthesis, Transaminases deficiency
- Abstract
Serine biosynthesis defects are autosomal recessive metabolic disorders resulting from the deficiency of any of the three enzymes involved in de novo serine biosynthesis, specifically phosphoglycerate dehydrogenase (PGDH), phosphoserine aminotransferase (PSAT), and phosphoserine phosphatase (PSP). In this study, we performed metabolomic profiling on 4 children with serine biosynthesis defects; 3 with PGDH deficiency and 1 with PSAT deficiency. The evaluations were performed at baseline and with serine and glycine supplementation. Metabolomic profiling performed at baseline showed low phospholipid species, including glycerophosphocholine, glycerophosphoethanolamine, and sphingomyelin. All children had low serine and glycine as expected. Low glycerophosphocholine compounds were found in 4 children, low glycerophosphoethanolamine compounds in 3 children, and low sphingomyelin species in 2 children. Metabolic profiling with serine and glycine supplementation showed normalization of most of the low phospholipid compounds in the 4 children. Phospholipids are the major component of plasma and intracellular membranes, and phosphatidylcholine is the most abundant phospholipid of all mammalian cell types and subcellular organelles. Phosphatidylcholine is of particular importance for the nervous system, where it is essential for neuronal differentiation. The observed low phosphatidylcholine species in children with serine biosynthesis defects that improved after serine supplementation, supports the role of serine as a significant precursor for phosphatidylcholine. The vital role that phosphatidylcholine has during neuronal differentiation and the pronounced neurological manifestations in serine biosynthesis defects suggest that phosphatidylcholine deficiency occurring secondary to serine deficiency may have a significant contribution to the development of the neurological manifestations in individuals with serine biosynthesis defects., (Copyright © 2017 Elsevier Inc. All rights reserved.)
- Published
- 2018
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