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.
Competing interests: None declared
An erratum to this chapter is available at 10.1007/8904_2015_540
An erratum to this chapter can be found at http://dx.doi.org/10.1007/8904_2016_540
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Acknowledgements
We would like to thank the patient and her family for their participation in this report and Dr. Angela Sun for her careful review of this manuscript.
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Communicated by: Nicole Wolf, MD PhD
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Synopsis
This novel report of phosphoserine phosphatase deficiency in an adult expands our understanding of serine deficiency syndrome and describes an important and treatable condition for practitioners to consider when evaluating patients with unexplained metabolic neuropathy.
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Heather M. Byers, Emily A. Malouf, Michael D. Weiss, Jie Feng, C. Ronald Scott, and Suman Jayadev declare that they have no conflicts of interest.
Robin L. Bennett is an author for John Wiley & Sons.
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This article does not contain any research studies with human or animal subjects performed by the any of the authors.
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Dr. Heather Byers prepared the manuscript. Heather Byers, Robin Bennett, Emily Malouf, Michael Weiss, Jie Feng, C. Ronald Scott, and Suman Jayadev participated in the clinical care of this patient and critical review of the manuscript.
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Byers, H.M. et al. (2015). Novel Report of Phosphoserine Phosphatase Deficiency in an Adult with Myeloneuropathy and Limb Contractures. In: Morava, E., Baumgartner, M., Patterson, M., Rahman, S., Zschocke, J., Peters, V. (eds) JIMD Reports, Volume 30. JIMD Reports, vol 30. Springer, Berlin, Heidelberg. https://doi.org/10.1007/8904_2015_510
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DOI: https://doi.org/10.1007/8904_2015_510
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