Neuropathological Findings in Short-Chain enoyl-CoA Hydratase 1 Deficiency (ECHS1D): Case Report and Differential Diagnosis

Short-chain enoyl-CoA hydratase 1 (ECHS1) is an enzyme that participates in the metabolism of valine, transforming methacrylyl-CoA in β–hydroxy–isobutyryl-CoA. There is an accumulation of intermediate acids and ammonium as a consequence of its deficit. This background generates a harmful environment for the brain causing neuronal death and severe brain lesions. We present a case of a 39 weeks newborn that died at 31 hours old. We found vacuolization in basal areas, brain stem, cerebellum and spinal cord white matter (spongiform myelinopathy). These vacuoles were periodic acid–Schiff stain negative, there were neither acompanion gliosis nor macrophagic reaction. These findings were suggestive of metabolism acid disorders. The final diagnosis was confirmed by genetic study by massive parallel sequencing, showing 2 previously described pathogenic variants (c.160C > T and c.394G > A) of short-chain enoyl-CoA hydratase 1 gene. To our knowledge, this is the first case reporting the histological changes in short-chain enoyl-CoA hydratase 1 deficiency. Histological study provides useful information to orientate the diagnostic and clarify the clinical manifestations, especially in hospitals where urine or blood samples are not taking routinely or where genetic studies may not be performed. Synopsis: The main neuropathological findings in Short-chain enoyl-CoA hydratase 1 deficiency are the presence of whitte matter vacuoles in basal areas, brain stem and spinal cord.