C Marelli1,2,3, S Badiou4,5, S Genestet6, L Larrieu7, P Damier8, W Camu9, M Planes10, M Koenig7, C Guissart7. 1. Department of Neurology, Expert Centre for Neurogenetic Diseases and Adult Mitochondrial and Metabolic Diseases, Gui de Chauliac University Hospital Montpellier, 80, Avenue A Fliche, 34295, Montpellier, France. c-marelli@chu-montpellier.fr. 2. Laboratoire de Génétique de Maladies Rares EA7402, Institut Universitaire de Recherche Clinique, Université de Montpellier, Montpellier, France. c-marelli@chu-montpellier.fr. 3. Inserm U1198 MMDN, Montpellier, France. c-marelli@chu-montpellier.fr. 4. Biochemistry Laboratory, Lapeyronie Hospital, Montpellier, France. 5. PhyMedExp, INSERM, CNRS, CHU de Montpellier, Université de Montpellier, Montpellier, France. 6. Hôpital de la Cavale Blanche, Service d'Explorations Fonctionnelles Neurologiques, CHRU de Brest, 29609, Brest, France. 7. Institut Universitaire de Recherche Clinique, Laboratoire de Génétique de Maladies Rares EA7402, Laboratoire de Génétique Moléculaire, University Hospital, Université de Montpellier, Montpellier, France. 8. Service de Neurologie, CHU de Nantes, Nantes, France. 9. Expert Center for Motor Neuron Diseases, Explorations Neurologiques, CHU and Université de Montpellier, Montpellier, France. 10. Service de Genetique Clinique, CHRU Morvan, 29609, Brest, France.
Abstract
INTRODUCTION: The ALDH18A1 gene, encoding delta-1-pyrroline-5-carboxylate synthase (P5CS), is responsible for an autosomal recessive disease with severe developmental delay; more recently, ALDH18A1 was found to be responsible for SPG9, an autosomal dominant (AD) spastic paraplegia. CASE REPORT: We report a three-generation family with AD SPG9, initially suspected because of low citrulline on fasting plasma amino acid chromatography (AAC). Interestingly, in two patients, the spastic paraplegia appeared during pregnancy. One subject presented a severe childhood-onset form while another subject had a mild late-onset disease. CONCLUSION: The description of this family is of particular interest: it highlights the possibility of transient or permanent aggravation of spastic paraplegia due to SPG9 during pregnancy, suggesting a direct link between neurological symptoms and amino acid defect in a period of higher requirements and the potential benefit of amino acid supplementation; it underscores the value of plasma citrulline on fasting plasma AAC as a biomarker for this disease; it shows the variable expression of the disease.
INTRODUCTION: The ALDH18A1 gene, encoding delta-1-pyrroline-5-carboxylate synthase (P5CS), is responsible for an autosomal recessive disease with severe developmental delay; more recently, ALDH18A1 was found to be responsible for SPG9, an autosomal dominant (AD) spastic paraplegia. CASE REPORT: We report a three-generation family with AD SPG9, initially suspected because of low citrulline on fasting plasma amino acid chromatography (AAC). Interestingly, in two patients, the spastic paraplegia appeared during pregnancy. One subject presented a severe childhood-onset form while another subject had a mild late-onset disease. CONCLUSION: The description of this family is of particular interest: it highlights the possibility of transient or permanent aggravation of spastic paraplegia due to SPG9 during pregnancy, suggesting a direct link between neurological symptoms and amino acid defect in a period of higher requirements and the potential benefit of amino acid supplementation; it underscores the value of plasma citrulline on fasting plasma AAC as a biomarker for this disease; it shows the variable expression of the disease.