An intractable epilepsy phenotype of ASNS novel mutation in two patients with asparagine synthetase deficiency

Ling Liu; Jing Wang; Haiyu Li; Yan Dong; Ying Li; Lei Xia; Bo Yang; Handuo Wang; Yiran Xu; Guomei Cheng; Kaixian Du; Xiaoli Zhang; Changlian Zhu; Shihong Cui; Chenchen Ren

doi:10.1016/j.cca.2022.04.989

An intractable epilepsy phenotype of ASNS novel mutation in two patients with asparagine synthetase deficiency

Clin Chim Acta. 2022 Jun 1:531:331-336. doi: 10.1016/j.cca.2022.04.989. Epub 2022 Apr 22.

Authors

Ling Liu¹, Jing Wang², Haiyu Li², Yan Dong³, Ying Li², Lei Xia³, Bo Yang², Handuo Wang², Yiran Xu⁴, Guomei Cheng⁵, Kaixian Du³, Xiaoli Zhang⁶, Changlian Zhu⁷, Shihong Cui⁸, Chenchen Ren⁹

Affiliations

¹ Department of Prenatal Diagnosis Center, The Third Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, Henan Province, China; NHC Key Laboratory of Birth Defects Prevention, Henan Key Laboratory of Population Defects Prevention, Henan Institute of Reproduction Health Science and Technology, No.26 Jingwu Road, Jinshui District, Zhengzhou 450002, Henan, China. Electronic address: liuling@zzu.edu.cn.
² Department of Prenatal Diagnosis Center, The Third Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, Henan Province, China.
³ Department of Pediatrics of The Third Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, Henan Province, China.
⁴ Henan Key Laboratory of Child Brain Injury and Henan Pediatric Clinical Research Center, Institute of Neuroscience and Third Affiliated Hospital and of Zhengzhou University, Zhengzhou 450052, Henan Province, China; NHC Key Laboratory of Birth Defects Prevention, Henan Key Laboratory of Population Defects Prevention, Henan Institute of Reproduction Health Science and Technology, No.26 Jingwu Road, Jinshui District, Zhengzhou 450002, Henan, China.
⁵ Department of Obstetrics and Gynecology, The Third Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, Henan Province, China.
⁶ Henan Key Laboratory of Child Brain Injury and Henan Pediatric Clinical Research Center, Institute of Neuroscience and Third Affiliated Hospital and of Zhengzhou University, Zhengzhou 450052, Henan Province, China.
⁷ Department of Pediatrics of The Third Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, Henan Province, China; Henan Key Laboratory of Child Brain Injury and Henan Pediatric Clinical Research Center, Institute of Neuroscience and Third Affiliated Hospital and of Zhengzhou University, Zhengzhou 450052, Henan Province, China.
⁸ Department of Prenatal Diagnosis Center, The Third Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, Henan Province, China; Department of Obstetrics and Gynecology, The Third Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, Henan Province, China.
⁹ Department of Obstetrics and Gynecology, The Third Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, Henan Province, China. Electronic address: renshenshen1106@126.com.

PMID: 35469797
DOI: 10.1016/j.cca.2022.04.989

Abstract

Background and objective: Asparagine synthetase deficiency (ASNSD) is a rare neurometabolic disease caused by variations of the ASNS gene. It manifests as microcephaly, severe developmental delay, and spastic quadriplegia. 71% of ASNSD patients died during early infancy. We aim to investigate mutations related to intractable epilepsy in one Chinese genealogy.

Material and methods: Head Magnetic Resonance Imaging (MRI), whole exome sequencing (WES), and Liquid Chromatography-Mass Spectrometry (LC-MS) to help 2 patients with intractable epilepsy find the underlying mechanisms of disease.

Results: These two patients had a compound heterozygous mutation (c.224A > G, p.N75S and c.1612A > G, p.M538V) in the ASNS gene, of which c.1612A > G was a novel mutation. The asparagine levels in patients' plasmas were normal. In addition, they had a later onset, longer survival, and were milder than previously reported ASNSD patients.

Conclusions: Two patients were diagnosed with a milder form of ASNSD. Clinically, the asparagine level in the patient's plasma cannot be used as the only basis to diagnose this disease. This study has expanded the disease phenotype spectrum of ASNSD and broadened the variation profile of the ASNS gene, which can assist in the clinical diagnosis and treatment of ASNSD patients.

Keywords: ASNS gene; Asparagine synthetase deficiency; Intractable epilepsy; Metabolic disease; Whole exome sequencing.

Publication types

Case Reports

MeSH terms

Amino Acid Metabolism, Inborn Errors*
Asparagine / genetics
Aspartate-Ammonia Ligase* / genetics
Drug Resistant Epilepsy*
Humans
Intellectual Disability* / genetics
Microcephaly* / genetics
Mutation
Neurodegenerative Diseases*
Phenotype

Substances

Asparagine
Aspartate-Ammonia Ligase