To the Editor: We appreciate Dr. Majid Arash’s interest in our article and insightful comments [
1,
2]. Our report detailed the case of an 11-mo-old male who experienced acute neuroregression following a febrile illness. The patient displayed tongue and orbicularis oris muscle fasciculations and brisk reflexes, which pointed to characteristics indicative of motor neuron disease (MND). Whole exome sequencing identified a pathogenic variant in the
GBA gene, which was subsequently validated through Sanger sequencing. Glucocerebrosidase activity was also reduced in leukocytes, further supporting the pathogenicity of the identified variant. We concur with Dr. Arash’s observations regarding potential causes, such as hypoglossal nerve damage, Möbius syndrome, or hypoxic-ischemic injury, which can present with similar symptoms in infants. However, in this case, the child’s brain MRI was normal, and there was no involvement of facial muscles except for external ophthalmoplegia. Based on a review of old videos, the child was developmentally normal before symptom onset, with no signs of ocular or facial muscle involvement. Gaucher disease is a genetic metabolic disorder due to lack of activity of the enzyme glucocerebrosidase in the lysosome, leading to the accumulation of lipids such as glucosylceramide and glucosyl sphingosine. Studies indicate that accumulating ceramides and cholesterol esters might contribute to the death of motor neurons in MND by promoting oxidative stress [
3]. Recent studies have revealed that glucosylceramide increases agonist-induced calcium release from intracellular stores through the ryanodine receptor, ultimately causing neuronal cell death. Abnormalities in the autophagy pathway have also been observed in patients with Gaucher disease, with evidence pointing to dysfunctional mitochondria and mTOR pathway dysregulation [
4]. We agree that co-occurrence with a specific disease is insufficient. Based on the available literature, we hypothesize that reduced GBA activity and glycolipid accumulation may directly correlate with the index case phenotype. …
