New Term Request: Glutamine deficiency, congenital

[vjenkinsFB]

I'd like to request a term for glutamine deficiency, congenital (this is what OMIM uses but less awkward terms are available, see below). Whether this should be two separate diseases or not, I will leave up to you.

OMIM: https://www.omim.org/entry/610015

Potential definition: Glutamine deficiency, congenital has_material_basis_in homozygous mutation in the gene GLUL on chromosome 1q25.

Potential parent term: amino acid metabolic disorder

Synonyms: glutamine synthase deficiency, congenital systemic; GLUL deficiency; Congenital brain dysgenesis due to glutamine synthetase deficiency

ClinVar search term: GLUL[gene] AND (1[VARLEN]:1000[VARLEN] AND "single gene"[Properties])

MedGen page(s) pointed to by the above: https://www.ncbi.nlm.nih.gov/medgen/C1864910 Congenital brain dysgenesis due to glutamine synthetase deficiency

MalaCards pages:

• https://www.malacards.org/card/glutamine_deficiency_congenital
• https://www.malacards.org/card/congenital_brain_dysgenesis_due_to_glutamine_synthetase_deficiency

HGNC entry for gene: https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:4341

Citations other than those in the OMIM entry:

• https://pubmed.ncbi.nlm.nih.gov/38416643/ Martelli F, Lin J, Mele S, et al. Identifying potential dietary treatments for inherited metabolic disorders using Drosophila nutrigenomics. Cell Rep. 2024;43(3):113861. doi:10.1016/j.celrep.2024.113861
• https://pubmed.ncbi.nlm.nih.gov/32888207/ Roifman M, Niles KM, MacNeil L, et al. Homozygous GLUL deletion is embryonically viable and leads to glutamine synthetase deficiency. Clin Genet. 2020;98(6):613-619. doi:10.1111/cge.13844
• https://pubmed.ncbi.nlm.nih.gov/27775558/ Spodenkiewicz M, Diez-Fernandez C, Rüfenacht V, Gemperle-Britschgi C, Häberle J. Minireview on Glutamine Synthetase Deficiency, an Ultra-Rare Inborn Error of Amino Acid Biosynthesis. Biology (Basel). 2016;5(4):40. Published 2016 Oct 19. doi:10.3390/biology5040040
• https://pubmed.ncbi.nlm.nih.gov/38579670/ Jones AG, Aquilino M, Tinker RJ, et al. Clustered de novo start-loss variants in GLUL result in a developmental and epileptic encephalopathy via stabilization of glutamine synthetase. Am J Hum Genet. 2024;111(4):729-741. doi:10.1016/j.ajhg.2024.03.005

FlyBase paper(s) to curate with this term: FBrf0259145

My contact info: vjenkins@morgan.harvard.edu (FlyBase), 0000-0002-1567-7626. Thank you!

[csbjohnson]

Hi @vjenkinsFB,

Thank you for your request . We'll review your new term request for Glutamine deficiency, congenital.

Best, Claudia Marie Sánchez-Beato Johnson

[allenbaron]

The name at OMIM might be a little general (it seems plausible that other congenital glutamine deficiency diseases could be identified) and, while the authors did use both names OMIM has, it likely was not the authors intention to associate this specific disease with this name. Still, clinicians tend to prefer names from OMIM for genetic diseases and one of our goals is to avoid unnecessary disease nomenclature expansion, so I've decided to stick with OMIM's name in this case.

The descriptions at Orphanet and OMIM appear to be in agreement. I don't see evidence for creating two diseases as MalaCards has. I do think that the Jones AG paper should probably be considered a separate disease given its different inheritance and presentation. OMIM has added it as 'DEVELOPMENTAL AND EPILEPTIC ENCEPHALOPATHY 116' (MIM: 620806). I'll curate and add that disease as well.

[allenbaron]

I've also decided not to include "Congenital brain dysgenesis due to glutamine synthetase deficiency" from Orphanet because I could not find it's use in publications or the "GLUL deficiency" synonym since it's use appears to be limited to model organisms and it's not always used as a disease name. If you feel like either of those is useful to you, I'd be happy to add them but I'd probably add them as related synonyms instead of exact ones.

[allenbaron]

The requested disease will be in the next release (out today) as 'congenital glutamine deficiency' (DOID:0070544). 'developmental and epileptic encephalopathy 116' (DOID:0070545) has also been added.