A Neuro-Metabolic Syndrome that Needs to Be Discovered: A Child with Late Onset Asparagine Synthetase Deficiency
- 6 December 2021
- journal article
- research article
- Published by Georg Thieme Verlag KG in Journal of Pediatric Epilepsy
- Vol. 11 (02), 061-064
- https://doi.org/10.1055/s-0041-1739488
Abstract
Asparagine synthetase (ASNS) deficiency is a rare inborn error of metabolism caused by a defect in ASNS—a gene encoding asparagine synthetase. It has mainly been described as a neurological phenotype manifesting as severe developmental delay, congenital microcephaly, spasticity, and refractory seizures; it is not associated with any specific dysmorphisms. ASNS deficiency leads to the inability to synthesize a nonessential amino acid in the brain, this explains why the symptoms are primarily neurological. The accumulation of aspartate/glutamate causes increased neuronal apoptosis leading to brain atrophy and increased neuronal excitability leading to seizures. Asparagine levels in plasma and cerebrospinal fluid are not reliable biomarkers for this disorder, therefore diagnosis is mainly obtained by molecular genetics. This disorder is associated with a poor prognosis and there is no treatment except supportive therapy. Prenatal diagnosis is possible. We report a case of a later onset form, c.146G > A (p.Arg49Gln) variant in the ASNS gene detected by molecular analysis using next-generation sequencing; the patient's clinical presentation included microcephaly, regression of developmental milestones, epilepsy, and hyperthermia. Received: 30 July 2021 Accepted: 30 September 2021 Publication Date: 06 December 2021 (online) © 2021. Thieme. All rights reserved. Georg Thieme Verlag KG Rüdigerstraße 14, 70469 Stuttgart, GermanyKeywords
This publication has 9 references indexed in Scilit:
- Epileptic encephalopathy with microcephaly in a patient with asparagine synthetase deficiency: a video‐EEG report∗Epileptic Disorders, 2019
- Molecular diagnosis of asparagine synthetase (ASNS) deficiency in two Indian families and literature review of 29 ASNS deficient casesGene, 2019
- Characterization of a novel variant in siblings with Asparagine Synthetase DeficiencyMolecular Genetics and Metabolism, 2018
- Asparagine synthetase: Function, structure, and role in diseaseOnline Journal of Public Health Informatics, 2017
- Asparagine Synthetase deficiency-report of a novel mutation and review of literatureMetabolic Brain Disease, 2017
- The history of progressive myoclonus epilepsiesEpileptic Disorders, 2016
- Deficiency of Asparagine Synthetase Causes Congenital Microcephaly and a Progressive Form of EncephalopathyNeuron, 2013
- Asparagine synthetase: regulation by cell stress and involvement in tumor biologyAmerican Journal of Physiology-Endocrinology and Metabolism, 2013
- Asparagine Synthetase ChemotherapyAnnual Review of Biochemistry, 2006