| Autor: |
El-Hattab AW; Division of Clinical Genetics and Metabolic Disorders, Pediatrics Department, Tawam Hospital, Al-Ain, United Arab Emirates., Shaheen R; Department of Genetics, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia., Hertecant J; Division of Clinical Genetics and Metabolic Disorders, Pediatrics Department, Tawam Hospital, Al-Ain, United Arab Emirates., Galadari HI; Department of Internal Medicine, College of Medicine and Health Sciences, UAE University, Al-Ain, United Arab Emirates., Albaqawi BS; Women Specialized Hospital, King Fahad Medical City, Riyadh, Saudi Arabia., Nabil A; Medical Research Institute, Alexandria University, Alexandria, Egypt., Alkuraya FS; 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. |
| Abstrakt: |
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. |
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