Epileptic encephalopathy with microcephaly in a patient with asparagine synthetase deficiency: a video-EEG report∗

Paola Costa, Caterina Zanus, Flavio Faletra, Giulia Ventura, Giulia Maria di Marzio, Chiara Cervesi, Marco Carrozzi

Research output: Contribution to journalArticlepeer-review


Asparagine synthetase deficiency is a rare autosomal recessive neurometabolic disorder caused by mutations in the asparagine synthetase gene. It is characterized by congenital microcephaly, intellectual disability, progressive cerebral atrophy, and intractable seizures. A decrease in asparagine in CSF or plasma guides subsequent investigations in some cases, but normal values are described in other cases. Therefore, reaching a diagnosis is challenging and relies on exome sequencing. We report the case of a child with progressive microcephaly, irritability, startle reflexes, and jitteriness since birth. Focal clonic and myoclonic seizures, status epilepticus, and infantile spasms appeared in the first months of life. At first, the EEG showed multifocal epileptic activity which later turned into modified hypsarrhythmia and discontinuous activity. Brain MRI showed brain atrophy, a simplified gyral pattern, and poor myelination. Plasma asparagine levels were normal. Due to remote parental consanguinity, a study of contiguous regions of runs of homozygosity was performed, showing a 5-Mb region (chr7:95629078–100679007) including the asparagine synthetase gene. The molecular analysis of this gene led to identification of a novel homozygous missense mutation, c.761G>T(p.Gly254Val), in our patient. The peculiar electroclinical phenotype may lead to diagnostic suspicion and molecular analysis which may benefit genetic counselling. [Published with video sequence].

Original languageEnglish
Pages (from-to)466-470
Number of pages5
JournalEpileptic Disorders
Issue number5
Publication statusPublished - Oct 1 2019


  • asparagine synthetase deficiency
  • EEG
  • electroclinical phenotype
  • molecular analysis

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology


Dive into the research topics of 'Epileptic encephalopathy with microcephaly in a patient with asparagine synthetase deficiency: a video-EEG report∗'. Together they form a unique fingerprint.

Cite this