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

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.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.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.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.