Hereditary Spastic Paraplegia Is a Common Phenotypic Finding in ARG1 Deficiency, P5CS Deficiency and HHH Syndrome: Three Inborn Errors of Metabolism Caused by Alteration of an Interconnected Pathway of Glutamate and Urea Cycle Metabolism.

ABSTRACT: Hereditary Spastic Paraplegias (HSPs) are a clinically and genetically heterogeneous group of neurodegenerative disorders characterized by a progressive rigidity and weakness of the lower limbs, caused by pyramidal tract lesions. As of today, 80 different forms of HSP have been mapped, 64 genes have been cloned, and new forms are constantly being described. HSPs represent an intensively studied field, and the functional understanding of the biochemical and molecular pathogenetic pathways are starting to be elucidated. Recently, dominant and recessive mutations in the ALDH18A1 gene resulting in the deficiency of the encoded enzyme (delta-1-pyrroline-5-carboxylate synthase, P5CS) have been pathogenetically linked to HSP. P5CS is a critical enzyme in the conversion of glutamate to pyrr

SUBMITTER: Panza E 

PROVIDER: S-EPMC6395431 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature