Affiliations: VUmc School of Medical Sciences, VU University of Amsterdam, Amsterdam, The Netherlands | University of Groningen, University Medical Center Groningen, Department of Genetics, Groningen, The Netherlands
Note:  Corresponding author: Dr. Tom J. de Koning, Department of Genetics, HP CB 50, University Medical Centre Groningen, PO Box 30.001, 9700 RB Groningen, The Netherlands. Tel.: +31 50 3617100; Fax: +31 50 3617230; E-mail: [email protected]
Abstract: Serine deficiency disorders are rare causes of seizures in infants and children caused by a genetic defect in one of the three genes coding for the L-serine biosynthesis pathway enzymes. A wide phenotypic spectrum can be observed in patients with serine deficiency disorders ranging from a lethal disorder with multiple congenital abnormalities to a congenital microcephaly and intractable seizures presenting shortly after birth or a relatively mild phenotype with childhood absence seizures. Serine deficiency disorders can be diagnosed by cerebrospinal fluid and plasma amino acid analysis or by mutation analysis of the three genes including phosphoglycerate dehydrogenase (PHGDH), phosphoserine aminotransferase 1 (PSAT1) and phosphoserine phosphatase (PSPHD). Prompt recognition of affected patients is important, since serine deficiency disorders are treatable causes of seizures. There is a very strict window-of-opportunity to prevent developmental delay in patients with infantile and juvenile onset of phenotypes. In this paper, we present an overview of the clinical phenotypes associated with serine deficiency disorders presenting in infancy and childhood.