Freua, Fernando;
Almeida, Mariana Espíndola de Castro;
Nóbrega, Paulo Ribeiro;
Paiva, Anderson Rodrigues Brandáo de;
Della-Ripa, Bruno;
Cunha, Paulina;
Macedo-Souza, Lúcia Inês;
... Kok, Fernando; + view all
(2022)
Arginase 1 deficiency presenting as complicated hereditary spastic paraplegia.
Molecular Case Studies
, Article mcs.a006232. 10.1101/mcs.a006232.
(In press).
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Abstract
INTRODUCTION: Argininemia or arginase deficiency is a metabolic disorder caused by pathogenic variants in ARG1 and consists of a variable association of progressive spastic paraplegia, intellectual disability, and seizures. Hereditary spastic paraplegia (HSP) is a group of inherited diseases whose main feature is a progressive gait disorder characterized by lower limb spasticity. This study presents 7 patients with arginase 1 deficiency from 6 different families, all with an initial diagnosis of complicated HSP. METHODS: We evaluated the clinical data of 7 patients belonging to six independent families who were diagnosed with hyperargininemia in a neurogenetics outpatient clinic. RESULTS: All patients had lower limb spasticity and six had global developmental delay. Five individuals had intellectual disability and two had epilepsy. Psychiatric abnormalities were seen in two patients. In two participants of this study, MRI disclosed thinning of the corpus callosum. Molecular diagnosis was made by whole exome sequencing. All variants were present in homozygosis; we identified two novel missense variants, one novel frameshift variant, and one previously published missense variant. DISCUSSION: Clinical diagnosis of early onset complicated hereditary spastic paraplegia was made in all patients. Two patients were initially suspected of having SPG11 due to thinning of the corpus callosum. As argininemia may present with a highly penetrant phenotype of spastic paraplegia associated with additional symptoms, this disease may represent a specific entity amongst the complicated HSPs.
| Type: | Article |
|---|---|
| Title: | Arginase 1 deficiency presenting as complicated hereditary spastic paraplegia |
| Location: | United States |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1101/mcs.a006232 |
| Publisher version: | https://doi.org/10.1101/mcs.a006232 |
| Language: | English |
| Additional information: | This article is distributed under the terms of the Creative Commons Attribution-NonCommercial License, which permits reuse and redistribution, except for commercial purposes, provided that the original author and source are credited. |
| Keywords: | Focal seizures with impairment of consciousness or awareness, Hypoargininemia, Intellectual disability, moderate, Progressive spastic paraparesis, Progressive spastic paraplegia, Spastic gait |
| UCL classification: | UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Department of Neuromuscular Diseases UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10157124 |
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