title: Phenotypic heterogeneity and adverse effects of serine treatment in 3-phosphoglycerate dehydrogenase deficiency: report on two siblings.
abstract: Clinical experience with the treatment of 3-phosphoglycerate dehydrogenase deficiency, a rare inherited disorder of serine synthesis, is scarce. We report on two sisters with phenotypic heterogeneity and a favourable response to combined serine and glycine supplementation. The elder sibling was found to be normocephalic at birth and showed moderate delay of white matter myelinisation, while her seizures arrested spontaneously even without treatment. In the younger sister with the classical phenotype, feeding difficulties with recurrent gastro-oesophageal reflux prompted us to treat her temporarily with high-dose serine (1400 mg/kg/day). An arrest of head growth then occurred but could be reversed by reducing the serine supply. In both children serine therapy was associated with decreased concentrations of methionine, isoleucine, and ornithine in the cerebrospinal fluid, attributed to competitive inhibition of neutral amino acid transport across the blood-brain barrier. In contrast to reports in the literature, these findings demonstrate that congenital microcephaly, intractable seizures, and dysmyelinisation are not invariably present in patients with 3-phosphoglycerate dehydrogenase deficiency. An adverse effect of high-dose serine therapy on head growth and on the transport of neutral amino acids across the blood-brain barrier should be considered and requires adjustment of treatment.
authors.affiliation: Division of Paediatric Neurology, Department of Paediatrics, University Hospital, RWTH, Aachen, Germany.
authors.forename: M G
authors.initials: MG
authors.lastname: Häusler
authors.forename: J
authors.initials: J
authors.lastname: Jaeken
authors.forename: E
authors.initials: E
authors.lastname: Mönch
authors.forename: V T
authors.initials: VT
authors.lastname: Ramaekers
mesh_terms: D000596:Amino Acids / Q000009:adverse effects* / Q000627:therapeutic use; D002237:Carbohydrate Dehydrogenases / Q000172:deficiency*; D002555:Cerebrospinal Fluid / Q000187:drug effects; D002648:Child; D002675:Child, Preschool; D004305:Dose-Response Relationship, Drug; D005260:Female; D005998:Glycine / Q000627:therapeutic use; D006257:Head / Q000254:growth & development; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008661:Metabolism, Inborn Errors / Q000175:diagnosis / Q000188:drug therapy* / Q000235:genetics*; D010641:Phenotype; D050543:Phosphoglycerate Dehydrogenase; D012694:Serine / Q000008:administration & dosage / Q000009:adverse effects* / Q000097:blood; D013036:Spasms, Infantile / Q000097:blood / Q000134:cerebrospinal fluid / Q000175:diagnosis / Q000188:drug therapy* / Q000235:genetics*; D016896:Treatment Outcome
chemical_list: D000596:Amino Acids; D012694:Serine; D002237:Carbohydrate Dehydrogenases; D050543:Phosphoglycerate Dehydrogenase; D005998:Glycine