title: Infantile Serine Biosynthesis Defect Due to Phosphoglycerate Dehydrogenase Deficiency: Variability in Phenotype and Treatment Response, Novel Mutations, and Diagnostic Challenges.
abstract: Serine biosynthesis defects can present in a broad phenotypic spectrum ranging from Neu-Laxova syndrome, a lethal disease with multiple congenital anomalies at the severe end, to an infantile disease with severe psychomotor retardation and seizures as an intermediate phenotype, to a childhood disease with intellectual disability at the mild end. In this report we present 6 individuals from 3 families with infantile phosphoglycerate dehydrogenase (PGDH) deficiency who presented with psychomotor delay, growth failure, microcephaly, and spasticity. The phenotype was variable with absence of seizures in 2 sisters in family 1 and 1 infant in family 2 and seizures with pronounced happy affect in 3 sisters in family 3. The initiation of serine treatment had pronounced effect on seizures and spasticity in the sisters in family 3, but minimal developmental effects on the children in families 1 and 2. With such phenotypic variability, the diagnosis of PGDH deficiency can be challenging.
authors.affiliation: 1 Joe DiMaggio Children's Hospital, Hollywood, FL, USA.|2 Florida Atlantic University Charles E. Schmidt College of Medicine, Boca Raton, FL, USA.
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Benke
authors.affiliation: 2 Florida Atlantic University Charles E. Schmidt College of Medicine, Boca Raton, FL, USA.
authors.forename: Ryan J
authors.initials: RJ
authors.lastname: Hidalgo
authors.affiliation: 3 Department of Radiology, Memorial Healthcare System, Hollywood, FL, USA.
authors.forename: Bruce H
authors.initials: BH
authors.lastname: Braffman
authors.affiliation: 4 Department of Genetics, University Medical Centre Utrecht, Utrecht, the Netherlands.
authors.forename: Judith
authors.initials: J
authors.lastname: Jans
authors.affiliation: 4 Department of Genetics, University Medical Centre Utrecht, Utrecht, the Netherlands.
authors.forename: Koen L I van
authors.initials: KLIV
authors.lastname: Gassen
authors.affiliation: 5 Pediatrics Medical Genetic Unit (PMGU), Pediatrics Department, Qatif Central Hospital, Qatif, Saudi Arabia.
authors.forename: Rawda
authors.initials: R
authors.lastname: Sunbul
authors.affiliation: 6 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
mesh_terms: D000015:Abnormalities, Multiple / Q000000981:diagnostic imaging / Q000209:etiology / Q000235:genetics / Q000628:therapy; D000293:Adolescent; D001927:Brain Diseases / Q000000981:diagnostic imaging / Q000209:etiology / Q000235:genetics / Q000628:therapy; D002239:Carbohydrate Metabolism, Inborn Errors / Q000150:complications* / Q000000981:diagnostic imaging / Q000235:genetics; D002675:Child, Preschool; D005192:Family Health; D005260:Female; D005317:Fetal Growth Retardation / Q000000981:diagnostic imaging / Q000209:etiology / Q000235:genetics / Q000628:therapy; D006801:Humans; D007057:Ichthyosis / Q000000981:diagnostic imaging / Q000209:etiology / Q000235:genetics / Q000628:therapy; D007223:Infant; D017880:Limb Deformities, Congenital / Q000000981:diagnostic imaging / Q000209:etiology / Q000235:genetics / Q000628:therapy; D008297:Male; D008831:Microcephaly / Q000150:complications* / Q000000981:diagnostic imaging / Q000209:etiology / Q000235:genetics / Q000628:therapy; D009154:Mutation / Q000235:genetics*; D010641:Phenotype; D050543:Phosphoglycerate Dehydrogenase / Q000172:deficiency* / Q000235:genetics*; D011596:Psychomotor Disorders / Q000150:complications* / Q000000981:diagnostic imaging / Q000235:genetics; D012640:Seizures / Q000150:complications* / Q000000981:diagnostic imaging / Q000235:genetics; D012694:Serine / Q000096:biosynthesis; D055815:Young Adult
chemical_list: D012694:Serine; D050543:Phosphoglycerate Dehydrogenase
keywords: Neu-Laxova syndrome; PGDH; microcephaly; seizures; spasticity