Deficiency of alkaline ceramidase 3 with infancy-onset progressive leukoencephalopathy: a second case report

Excerpt

Ceramides are hydrolyzed to free fatty acid and sphingosine by alkaline ceramidase, which is encoded by ACER3. Free fatty acid and sphingosine are essential molecules for complex sphingolipid synthesis, which maintains the function and integrity of cell membranes [1]. The metabolism of sphingolipids, particularly ceramides play a crucial role for normal brain development and function [2]. This significance of alkaline ceramidase 3 (ACER3) in human physiology, was for the first time explored by a recent study which demonstrated that deficiency of ACER3 with subsequent aberrant accumulation of ceramides are found to be associated with progressive leukodystophy in early childhood. This study showed that homozygous loss of function p.E33G mutation in ACER3 gene caused an impairment in the activity of ACER3 ceramidases. Higher levels of ACER3 preferred ceramides, especially C18:1 and C20:1 ceramides, have been demonstrated in patients compared to healthy subjects. These abnormal levels of ceramides have been proposed to impair central myelination process, which is responsible from the clinical manifestations in these patients [3]. …