Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2015:22:11-6.
doi: 10.1007/8904_2014_405. Epub 2015 Feb 8.

Asparagine Synthetase Deficiency: New Inborn Errors of Metabolism

Majid Alfadhel  1 , Muhammad Talal Alrifai, Daniel Trujillano, Hesham Alshaalan, Ali Al Othaim, Shatha Al Rasheed, Hussam Assiri, Abdulrhman A Alqahtani, Manal Alaamery, Arndt Rolfs, Wafaa Eyaid
Affiliations

Asparagine Synthetase Deficiency: New Inborn Errors of Metabolism

Majid Alfadhel et al. JIMD Rep. 2015.

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.

PubMed Disclaimer

Figures

Fig. 1
Fig. 1
Brain MRI of a 14-day-old girl (a–c). (a) Sagittal T1 shows severe microcephaly and cerebral atrophy. (b) Axial T1 shows simplified gyriform pattern of the frontal lobes with delayed myelination. (c) Axial T2 shows normal basal ganglia. Brain MRI of a 4-month-old boy (d–g). (d) Sagittal T1 shows severe microcephaly and cerebral atrophy. (e, f) Axial T1 shows simplified gyriform pattern of the frontal lobes with delayed myelination. (g) Axial T2 shows normal basal ganglia, frontal lobes simplified gyriform pattern, and delayed myelination
Fig. 2
Fig. 2
Subtle dysmorphic features: microcephaly, brachycephaly, pear-like head shape, micrognathia, and axial hypotonia (a–d)
Fig. 3
Fig. 3
Asparagine synthetase enzyme converts aspartate to asparagine in the presence of glutamine which is the amino group donor in this reaction
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Ben-Salem S, Gleeson JG, Al-Shamsi AM et al (2014) Asparagine synthetase deficiency detected by whole exome sequencing causes congenital microcephaly, epileptic encephalopathy and psychomotor delay. Metab Brain Dis. doi:10.1007/s1011-014-9618-0 - PMC - PubMed
    1. Bourgeron T, Chretien D, Poggi-Bach J, et al. Mutation of the fumarase gene in two siblings with progressive encephalopathy and fumarase deficiency. J Clin Invest. 1994;93:2514. doi: 10.1172/JCI117261. - DOI - PMC - PubMed
    1. Haberle J, Gorg B, Rutsch F, et al. Congenital glutamine deficiency with glutamine synthetase mutations. N Engl J Med. 2005;353:1926–1933. doi: 10.1056/NEJMoa050456. - DOI - PubMed
    1. Hongo S, Chiyo T, Takeda M. Cloning of cDNA for asparagine synthetase from rat Sertoli cell. Biochem Mol Biol Int. 1996;38:189–196. - PubMed
    1. Ruzzo EK, Capo-Chichi J-M, Ben-Zeev B, et al. Deficiency of asparagine synthetase causes congenital microcephaly and a progressive form of encephalopathy. Neuron. 2013;80:429–441. doi: 10.1016/j.neuron.2013.08.013. - DOI - PMC - PubMed

LinkOut - more resources