Autosomal dominant SPG9: intrafamilial variability and onset during pregnancy
- PDF / 544,474 Bytes
- 3 Pages / 595.276 x 790.866 pts Page_size
- 48 Downloads / 239 Views
BRIEF COMMUNICATION
Autosomal dominant SPG9: intrafamilial variability and onset during pregnancy C. Marelli 1,2,3 & S. Badiou 4,5 & S. Genestet 6 & L. Larrieu 7 & P. Damier 8 & W. Camu 9 & M. Planes 10 & M. Koenig 7 & C. Guissart 7 Received: 7 December 2019 / Accepted: 13 March 2020 # Fondazione Società Italiana di Neurologia 2020
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. Keywords Genetics . Metabolic diseases (inherited) . Spastic paraplegia
Short report A 39-year-old woman consulted because of spastic paraplegia, which appeared as progressive fatigue and leg stiffness during her first pregnancy, at the age of 28. After delivery, the symptoms persisted and were aggravated after a fall with double malleolus fracture; 1 year later, she required two canes, and 4 years later, she was wheelchair-bound. Neurological examination showed tetra-hyperreflexia with severe lower limb spasticity and weakness and distal upper limb weakness with thenar hypotrophy. She had short stature and no cognitive impairment. * C. Marelli [email protected] 1
2
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 Laboratoire de Génétique de Maladies Rares EA7402, Institut Universitaire de Recherche Clinique, Université de Montpellier, Montpellier, France
3
Inserm U1198 MMDN, Montpellier, France
4
Biochemistry Laboratory, Lapeyronie Hospital, Montpellier, France
Her sister also suffers from spastic paraplegia, still allowing autonomous walking, which appeared during her 4th pregnancy, at the age of 37 years. The eldest child of the sister suffers from global severe motor and cognitive developmental delay with microcephaly, short stature, epilepsy, ataxia, and spasticity; no problems were reported during pregnancy and delivery. The proband’s mother also suffers from progressive spastic pa
Data Loading...
