In a study involving an Egyptian cohort of patients with neuronopathic Gaucher disease, researchers observed that patients show diverse clinical outcomes that are markedly different from those exhibited by patients in other countries. The results are summarized in a study titled “Long-term follow-up and sudden unexpected death in Gaucher disease type 3 in Egypt,” and published in the journal Neurology: Genetics.
Gaucher disease type 3, also known as chronic neuronopathic Gaucher disease, is known to affect approximately 5 percent of patients with Gaucher disease in the United States and Europe. Recent reports suggest that in countries such as China, Korea, and Egypt, Gaucher disease type 3 is actually the predominant disease form. The type 3 form of the disease is characterized by severe systemic disease and supranuclear gaze palsy (i.e., an inability to look in a particular direction as a result of cerebral impairment) accompanied by cognitive deficit.
In this study, the authors performed a prospective cohort study of 78 patients with Gaucher disease type 3 from Egypt under enzyme replacement therapy, following patients for up to nine years. Patients exhibited a genetically homogeneous background — about 80 percent of patients had the common neuronopathic Gaucher genotype L444P/L444P. Only patients on enzyme replacement therapy were included in this study to assure that their neurologic clinical phenotype was only due to intrinsic cerebral dysfunction, therefore excluding any contribution by visceral disease.
The researchers observed that this cohort of patients exhibited the complete clinical spectrum of this genotype with patients presenting a normal neurologic phenotype, while others exhibited severe neurologic manifestations.
In general, the patients presented marked behavioral abnormalities: common bulbar dysfunction (dysarthria, dysphagia, or stridor); epilepsy; and even frequent sudden unexpected death.
In this cohort of patients, the clinical phenotype was more severe and different when compared to that described for the same genotype in other countries.
The authors concluded that despite carrying the most common GBA1 genotype associated with neuronopathic Gaucher disease, this cohort of Egyptian patients under enzyme replacement therapy presented both phenotypes and clinical outcomes different from those observed in type 3 patients in other countries. So, identifying the underlying causes for these differences, such as genetic variants, will help researchers develop better therapies for neuronopathic Gaucher disease.