title: Novel Report of Phosphoserine Phosphatase Deficiency in an Adult with Myeloneuropathy and Limb Contractures.
abstract: Serine is a nonessential amino acid that plays a vital role in proper development and functioning of the central nervous system (CNS). Serine deficiency leads to microcephaly, intellectual disability, seizures, and psychomotor retardation in children and severe axonal neuropathy in adults. Serine deficiency syndrome is due to a deficiency of one of three enzymes in the endogenous serine biosynthesis pathway: phosphoglycerate dehydrogenase, phosphoserine transaminase, or, most rarely, phosphoserine phosphatase. Of critical importance to clinical care, serine deficiency syndrome is treatable. Herein, we describe the novel presentation of phosphoserine phosphatase deficiency in an adult. The patient had intrauterine growth restriction, lifelong intellectual disability, childhood onset epilepsy, and borderline microcephaly. In adulthood, she developed progressively severe lower extremity hypertonia, axonal neuropathy, and hand contractures. Neuropathy was complicated by non-healing wounds. Fasting plasma amino acids showed low serine and glycine. Molecular analysis revealed compound heterozygous mutations in phosphoserine phosphatase (PSPH). Treatment with oral serine resulted in improvement of plasma serine levels, decreased neuropathic pain, and subjective improvement in energy level. Although the first case of phosphoserine phosphatase deficiency was described nearly 20 years ago, only eight cases have been reported, all in children. This is the first report of phosphoserine phosphatase deficiency in an adult.
authors.affiliation: Division of Medical Genetics, University of Washington Medical Center, Seattle, WA, USA.
authors.forename: Heather M
authors.initials: HM
authors.lastname: Byers
authors.affiliation: Division of Medical Genetics, University of Washington Medical Center, Seattle, WA, USA.
authors.forename: Robin L
authors.initials: RL
authors.lastname: Bennett
authors.affiliation: Division of Medical Genetics, University of Washington Medical Center, Seattle, WA, USA.
authors.forename: Emily A
authors.initials: EA
authors.lastname: Malouf
authors.affiliation: Department of Neurology, University of Washington Medical Center, Seattle, WA, USA.
authors.forename: Michael D
authors.initials: MD
authors.lastname: Weiss
authors.affiliation: Division of Medical Genetics, University of Washington Medical Center, Seattle, WA, USA.|Division of Molecular Medicine, University of Washington Medical Center, Seattle, WA, USA.
authors.forename: Jie
authors.initials: J
authors.lastname: Feng
authors.affiliation: Division of Medical Genetics, University of Washington Medical Center, Seattle, WA, USA.|Division of Molecular Medicine, University of Washington Medical Center, Seattle, WA, USA.
authors.forename: C Ronald
authors.initials: CR
authors.lastname: Scott
authors.affiliation: Division of Medical Genetics, University of Washington Medical Center, Seattle, WA, USA. sumie@uw.edu.|Department of Neurology, University of Washington Medical Center, Seattle, WA, USA. sumie@uw.edu.
authors.forename: Suman
authors.initials: S
authors.lastname: Jayadev