Intracranial calcifications in DEGS1-Related Leukodystrophy: a potentially under-recognised neuroimaging feature

Pathogenic variants in DEGS1, encoding a sphingolipid desaturase critical for ceramide biosynthesis, disrupt sphingolipid homeostasis and oligodendrocyte function, leading to abnormal myelination. We report an infant with genetically confirmed DEGS1-related leukodystrophy (homozygous c.337A > C, p.Asn113His) who presented with abnormal eye movements and early-onset developmental arrest. This was accompanied by axial hypotonia, severe feeding difficulties, and refractory epilepsy, including epileptic spasms with modified hypsarrhythmia. Brain MRI demonstrated diffuse abnormal myelination per age, thin corpus callosum, and cerebellar involvement. Notably, susceptibility-weighted imaging suggested cerebellar white matter calcifications, which were confirmed on brain CT, alongside punctate supratentorial calcifications, an atypical finding for DEGS1-related disease. This case expands the neuroimaging phenotype of DEGS1-related leukodystrophy and highlights intracranial calcifications, particularly within the cerebellum, as a potential diagnostic clue in the differential diagnosis of hypomyelinating disorders with conatal onset. Our findings also underscore the severe clinical course associated with DEGS1 deficiency, including profound developmental impairment, early-onset epilepsy, and persistent feeding difficulties.