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Clinical status, biochemical profile and management of a single cohort of patients with arginase deficiency.

Keshavan, Nandaki; Wood, Michelle; Alderson, Lucy M; Cortina-Borja, Mario; Skeath, Rachel; McSweeney, Mel; Dixon, Marjorie; ... Batzios, Spyros; + view all (2022) Clinical status, biochemical profile and management of a single cohort of patients with arginase deficiency. JIMD Reports , 63 (2) pp. 123-130. 10.1002/jmd2.12266. Green open access

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Abstract

Arginase deficiency is a rare autosomal recessive urea cycle disorder (UCD) caused by mutations in the ARG1 gene encoding arginase that catalyses the hydrolysis of arginine to ornithine and urea. Patients have hyperargininaemia and progressive neurological impairment but generally suffer fewer metabolic decompensations compared to other UCDs. The objective is to describe the clinical features, biochemical profile, neuroradiological findings and experience of managing children with arginase deficiency. Twenty-year retrospective review of patient medical records at a single metabolic centre was performed. Six patients from three unrelated families were identified. Mean age at first symptom was 3.3 (1.5-9.0) years, while mean age at diagnosis was 8.8 (0.16-15.92) years. Four patients developed spastic diplegia and two of six with spastic quadriplegia with classical features including hyperreflexia, clonus and toe walking. This resulted in gait abnormalities that have been monitored using the GAITRite system and required Achilles tendon release in five children. Generalised tonic-clonic seizures and/or absences were present in three of six children and were controlled with anticonvulsants. All patients had moderate learning difficulties. Neuroimaging showed cerebral/cerebellar atrophy in four patients and basal ganglia abnormalities in two. Arginine levels were universally elevated throughout follow-up despite protein restriction, essential amino acid supplementation and ammonia scavengers, and neurological outcome was generally poor. Two patients died following severe metabolic decompensation in adolescence. Children with arginase deficiency continue to present a management challenge of what appears to be an inexorable course of neurocognitive impairment. Further insight into disease mechanisms may provide insight into novel treatment strategies.

Type: Article
Title: Clinical status, biochemical profile and management of a single cohort of patients with arginase deficiency.
Location: United States
Open access status: An open access version is available from UCL Discovery
DOI: 10.1002/jmd2.12266
Publisher version: https://doi.org/10.1002/jmd2.12266
Language: English
Additional information: © 2021 The Authors. JIMD Reports published by John Wiley & Sons Ltd on behalf of SSIEM. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
Keywords: arginase deficiency, hyperammonaemia, metabolic decompensation, trial end points, urea cycle disorder
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health > Genetics and Genomic Medicine Dept
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
URI: https://discovery.ucl.ac.uk/id/eprint/10145373
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