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A Serine Synthesis Defect Presenting With a Charcot-Marie-Tooth–Like Polyneuropathy

Aurélie Méneret, MD; Elsa Wiame, PhD; Cecilia Marelli, MD; Timothée Lenglet, MD; Emile Van Schaftingen, MD, PhD; Frédéric Sedel, MD, PhD
Arch Neurol. 2012;69(7):908-911. doi:10.1001/archneurol.2011.1526.
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Background  Serine synthesis defects, characterized by developmental delay and seizures, have been described in children.

Objective  To describe a case of serine synthesis defect due to 3-phosphoglycerate dehydrogenase deficiency in an adult with prominent chronic polyneuropathy.

Design  Case report.

Setting  Neurologic referral center.

Patient  A 31-year-old man with congenital cataracts, mild psychomotor retardation, slight cerebellar ataxia, and chronic axonal sensorimotor polyneuropathy.

Interventions  Electrophysiologic, metabolic, and genetic testing and treatment with oral L-serine.

Main Outcome Measures  Serine values in plasma and cerebrospinal fluid and clinical examination.

Results  Amino acid analysis showed low serine levels in plasma and cerebrospinal fluid, and genetic analysis revealed 2 heterozygous mutations in the PGDH gene. Treatment with high-dose serine resulted in normalization of plasma serine values and subjective functional improvement.

Conclusions  This case expands the phenotypic spectrum of 3-phosphoglycerate dehydrogenase deficiency. Plasma amino acid chromatography should be added to the list of investigations performed in patients with Charcot-Marie-Tooth–like polyneuropathy, especially if it is associated with psychomotor delay and congenital cataracts.

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Grahic Jump Location

Figure 1. The phosphorylated L-serine biosynthesis pathway. 3-PGDH indicates 3-phosphoglycerate dehydrogenase; PSAT, phosphoserine aminotransferase; PSPH, phosphoserine phosphatase; and SHMT, serine hydroxymethyltransferase.

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Grahic Jump Location

Figure 2. Mutational analysis of the patient and his parents. Two heterozygous mutations, c.1273G>A (p.Val425Met) in exon 11 (inherited from the father) and c.1471C>T (p.Arg491Trp) in exon 12 (inherited from the mother), were found in the PGDH gene.

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