%0 Review
%T DEGS1 -related leukodystrophy: a clinical report and review of literature.
%A Wong MST
%A Thomas T
%A Lim JY
%A Kam S
%A Teo JX
%A Ching J
%A Goh CYJ
%A Jamuar SS
%A Lim WK
%A Koh AL
%J Clin Dysmorphol
%V 32
%N 3
%D 2023 Jul 1
%M 37195341
%F 0.884
%R 10.1097/MCD.0000000000000457
%X <B>BACKGROUND: </B>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.<BR><B>METHODS: </B>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.<BR><B>RESULTS: </B>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.<BR><B>CONCLUSIONS: </B>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.