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On the phenotypic spectrum of serine biosynthesis defects

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Journal of Inherited Metabolic Disease

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.

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    Authors and Affiliations

    1. Division of Clinical Genetics and Metabolic Disorders, Pediatrics Department, Tawam Hospital, Al-Ain, United Arab Emirates

      Ayman W. El-Hattab & Jozef Hertecant

    2. Department of Genetics, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia

      Ranad Shaheen & Fowzan S. Alkuraya

    3. Department of Internal Medicine, College of Medicine and Health Sciences, UAE University, Al-Ain, United Arab Emirates

      Hassan I. Galadari

    4. Women Specialized Hospital, King Fahad Medical City, Riyadh, Saudi Arabia

      Badi S. Albaqawi

    5. Medical Research Institute, Alexandria University, Alexandria, Egypt

      Amira Nabil

    6. Department of Anatomy and Cell Biology, College of Medicine, Alfaisal University, Riyadh, Saudi Arabia

      Fowzan S. Alkuraya

    7. College of Medicine, King Saud University, Riyadh, Saudi Arabia

      Fowzan S. Alkuraya

    8. Developmental Genetics Unit, Department of Genetics, King Faisal Specialist Hospital and Research Center, MBC-03, P.O. Box 3354, Riyadh, 11211, Saudi Arabia

      Fowzan S. Alkuraya

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    1. Ayman W. El-Hattab
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    Correspondence to Fowzan S. Alkuraya.

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    Ayman W. El-Hattab, Ranad Shaheen, Jozef Hertecant, Hassan I. Galadari, Badi S. Albaqawi, Amira Nabil, and Fowzan S Alkuraya declare that they have no conflict of interest.

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    All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and with the Helsinki Declaration of 1975, as revised in 2000 (5). Informed consent was obtained from all patients for being included in the study.

    Additional informed consent was obtained from all patients for which identifying information is included in this article.

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    Communicated by: Ertan Mayatepek

    Ayman W. El-Hattab and Ranad Shaheen contributed equally to this work.

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    El-Hattab, A.W., Shaheen, R., Hertecant, J. et al. On the phenotypic spectrum of serine biosynthesis defects. J Inherit Metab Dis 39, 373–381 (2016). https://doi.org/10.1007/s10545-016-9921-5

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