Abstract
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.
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Communicated by: Jutta Gaertner
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Take-Home Message
Asparagine synthetase deficiency is characterized by severe congenital microcephaly followed by childhood global developmental delay, central hypotonia, spastic quadriplegia and intractable seizure disorder. CSF asparagine level is low in this disorder while plasma may be low. Brain MRI showed microcephaly, brain atrophy, and delayed myelination and simplified gyriform pattern.
Conflict of Interest
Majid Alfadhel, Muhammad Talal Alrifai, Daniel Trujillano, Hesham Alshaalan, Ali Al Othaim, Shatha Al Rasheed, Hussam Assiri, Abdulrhman A Alqahtani, Manal Alaamery, Arndt Rolfs, and Wafaa Eyaid declare that they have no conflict of interest.
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Informed consent was obtained from parents of the patients included in the study. Proof that informed consent was obtained is available upon request.
Authors’ Contributions
MAF performed the majority of work associated with preparing, writing, and submitting the manuscript and contributed to the clinical diagnosis and management of the patients. MTR edited the manuscript and contributed to the clinical diagnosis and management of the patients. DT performed the molecular testing and contributed to the diagnosis of the patients and editing the manuscript. HA assessed and described the radiological findings obtained from the patients. AA edited the manuscript and contributed to biochemical investigations of the patients. SR edited the manuscript and contributed to clinical management of the patients. HAS summarized the clinical findings and contributed to the writing of the first draft. AQ summarized the clinical findings and contributed to the writing of the first draft. AR edited the manuscript, performed the molecular testing, and contributed to the diagnosis of the patients. WE edited the manuscript and contributed to the clinical diagnosis and management of the patients.
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Alfadhel, M. et al. (2015). Asparagine Synthetase Deficiency: New Inborn Errors of Metabolism. In: Zschocke, J., Baumgartner, M., Morava, E., Patterson, M., Rahman, S., Peters, V. (eds) JIMD Reports, Volume 22. JIMD Reports, vol 22. Springer, Berlin, Heidelberg. https://doi.org/10.1007/8904_2014_405
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DOI: https://doi.org/10.1007/8904_2014_405
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