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Review
. 2023 Jul 1;32(3):106-111.
doi: 10.1097/MCD.0000000000000457. Epub 2023 May 1.

DEGS1 -related leukodystrophy: a clinical report and review of literature

Melissa Song Ting Wong  1 , Terrence Thomas  2   3 , Jiin Ying Lim  3   4   5 , Sylvia Kam  3   4   5 , Jing Xian Teo  6 , Jianhong Ching  7   8 , Chew Yin Jasmine Goh  9 , Saumya Shekhar Jamuar  1   3   4   5   6 , Weng Khong Lim  5   6 , Ai Ling Koh  1   3   4   5
Affiliations
Review

DEGS1 -related leukodystrophy: a clinical report and review of literature

Melissa Song Ting Wong et al. Clin Dysmorphol. .

Abstract

Background: Leukodystrophies are a heterogeneous group of disorders affecting the white matter of the central nervous system, with or without affecting the peripheral nervous system. Biallelic variants in DEGS1 , coding for desaturase 1 (Des1) protein, were recently reported to be associated with hypomyelinating leukodystrophy (HLD), a subclass of leukodystrophies where the formation of the myelin sheath is affected.

Methods: Genomic sequencing was performed on our index patient with severe developmental delay, severe failure to thrive, dystonia, seizures, and hypomyelination on brain imaging. Sphingolipid analysis was performed and dihydroceramide/ceramide (dhCer/Cer) ratios were obtained by the measurement of ceramide and dihydroceramide species.

Results: A homozygous missense variant was identified in DEGS1 (c.565A > G:p Asn189Asp). The identified DEGS1 variant has been annotated as "conflicting reports of pathogenicity" on ClinVar. Follow-up sphingolipid analysis on our patient showed significantly raised dhCer/Cer and this was consistent with dysfunction of the Des1 protein, providing additional evidence to support the pathogenicity of this variant.

Conclusion: While rare, pathogenic variants in DEGS1 should be considered in patients with HLD phenotype. To date, 25 patients have been reported across four studies on DEGS1 -related HLD, and, in this report, we summarize the literature. More such reports will enable deeper phenotypic characterization of this disorder.

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