JIMD Reports, Volume 22

Majid Alfadhel, Muhammad Talal Alrifai, Daniel Trujillano, Hesham Alshaalan, Ali Al Othaim, Shatha Al Rasheed, Hussam Assiri, Abdulrhman A. Alqahtani, Manal Alaamery, Arndt Rolfs, Wafaa Eyaid, Alfadhel, Majid, Alrifai, Muhammad Talal, Trujillano, Daniel, Alshaalan, Hesham, Al Othaim, Ali, Al Rasheed, Shatha, Assiri, Hussam, Alqahtani, Abdulrhman A., Alaamery, Manal, Rolfs, Arndt, Eyaid, Wafaa

Background: Asparagine synthetase deficiency (ASD) is a newly identified neurometabolic disorder characterized by severe congenital microcephaly, severe global developmental delay, intractable seizure disorder, and spastic quadriplegia. Brain MRI showed brain atrophy, delayed myelination, and simplified gyriform pattern. Methods: We report ASD deficiency in a 2- and 4-year-old sibling. On them, we described clinical, biochemical, and molecular findings, and we compared our results with previously reported cases. Results: We identified a homozygous novel missense mutation in ASNS gene in both probands and we demonstrated low CSF and plasma asparagine in both patients. Conclusions: Clinicians should suspect ASD deficiency in any newborn presented with severe congenital microcephaly followed by severe epileptic encephalopathy and global developmental delay. CSF asparagine level is low in this disorder while plasma may be low.