title: On the phenotypic spectrum of serine biosynthesis defects.
abstract: L-serine is a non-essential amino acid that is de novo synthesized via the enzymes phosphoglycerate dehydrogenase (PGDH), phosphoserine aminotransferase (PSAT), and phosphoserine phosphatase (PSP). Besides its role in protein synthesis, L-serine is a precursor of a number of important compounds. Serine biosynthesis defects result from deficiencies in PGDH, PSAT, or PSP and have a broad phenotypic spectrum ranging from Neu-Laxova syndrome, a lethal multiple congenital anomaly disease at the severe end to a childhood disease with intellectual disability at the mild end, with infantile growth deficiency, and severe neurological manifestations as an intermediate phenotype. In this report, we present three subjects with serine biosynthesis effects. The first was a stillbirth with Neu-Laxova syndrome and a homozygous mutation in PHGDH. The second was a neonate with growth deficiency, microcephaly, ichthyotic skin lesions, seizures, contractures, hypertonia, distinctive facial features, and a homozygous mutation in PSAT1. The third subject was an infant with growth deficiency, microcephaly, ichthyotic skin lesions, anemia, hypertonia, distinctive facial features, low serine and glycine in plasma and CSF, and a novel homozygous mutation in PHGDH gene. Herein, we also review previous reports of serine biosynthesis defects and mutations in the PHGDH, PSAT1, and PSPH genes, discuss the variability in the phenotypes associated with serine biosynthesis defects, and elaborate on the vital roles of serine and the potential consequences of its deficiency.
authors.affiliation: Division of Clinical Genetics and Metabolic Disorders, Pediatrics Department, Tawam Hospital, Al-Ain, United Arab Emirates.
authors.forename: Ayman W
authors.initials: AW
authors.lastname: El-Hattab
authors.affiliation: Department of Genetics, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia.
authors.forename: Ranad
authors.initials: R
authors.lastname: Shaheen
authors.affiliation: Division of Clinical Genetics and Metabolic Disorders, Pediatrics Department, Tawam Hospital, Al-Ain, United Arab Emirates.
authors.forename: Jozef
authors.initials: J
authors.lastname: Hertecant
authors.affiliation: Department of Internal Medicine, College of Medicine and Health Sciences, UAE University, Al-Ain, United Arab Emirates.
authors.forename: Hassan I
authors.initials: HI
authors.lastname: Galadari
authors.affiliation: Women Specialized Hospital, King Fahad Medical City, Riyadh, Saudi Arabia.
authors.forename: Badi S
authors.initials: BS
authors.lastname: Albaqawi
authors.affiliation: Medical Research Institute, Alexandria University, Alexandria, Egypt.
authors.forename: Amira
authors.initials: A
authors.lastname: Nabil
authors.affiliation: Department of Genetics, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia. falkuraya@kfshrc.edu.sa.|Department of Anatomy and Cell Biology, College of Medicine, Alfaisal University, Riyadh, Saudi Arabia. falkuraya@kfshrc.edu.sa.|College of Medicine, King Saud University, Riyadh, Saudi Arabia. falkuraya@kfshrc.edu.sa.|Developmental Genetics Unit, Department of Genetics, King Faisal Specialist Hospital and Research Center, MBC-03, P.O. Box 3354, Riyadh, 11211, Saudi Arabia. falkuraya@kfshrc.edu.sa.
authors.forename: Fowzan S
authors.initials: FS
authors.lastname: Alkuraya
mesh_terms: D000015:Abnormalities, Multiple / Q000235:genetics*; D001927:Brain Diseases / Q000235:genetics*; D005317:Fetal Growth Retardation / Q000235:genetics*; D006801:Humans; D007057:Ichthyosis / Q000235:genetics*; D007223:Infant; D007231:Infant, Newborn; D017880:Limb Deformities, Congenital / Q000235:genetics*; D008297:Male; D008831:Microcephaly / Q000235:genetics*; D009154:Mutation / Q000235:genetics; D010641:Phenotype; D050543:Phosphoglycerate Dehydrogenase / Q000235:genetics*; D010744:Phosphoric Monoester Hydrolases / Q000235:genetics*; D012694:Serine / Q000096:biosynthesis* / Q000235:genetics*; D000637:Transaminases / Q000235:genetics*
chemical_list: D012694:Serine; D050543:Phosphoglycerate Dehydrogenase; D000637:Transaminases; C022393:phosphoserine aminotransferase; D010744:Phosphoric Monoester Hydrolases; C022394:phosphoserine phosphatase