Genetic variant reanalysis reveals a case of Sandhoff disease with onset of infantile epileptic spasm syndrome

Background Sandhoff disease(SD)i s an autosomal recessive lysosomal disease with clinical manifestations such as epilepsy,psychomotor retardation and developmental delay.However,infantile SD with onset of infantile epilepsy spasm syndrome(IESS)is extremely rare.Case presentation The case presented here was a 22-month-old boy,who presented with IESS and psychomotor retardation/regression at 6 months of age.The patient showed progressive aggravation of seizures and excessive startle responses.The whole exome sequencing data,which initially revealed negative results,were reanalyzed and indicated a homozygous mutation at the c.1613+4del splice site of the HEXB gene.The activities ofβ-hexosaminidase A and total hexosaminidase were significantly decreased.The fundus examination showed cherry red spots at the macula.Conclusions IESS can be an epileptic phenotype of infantile SD.Clinical phenotypes should be adequately collected in genetic testing.In the case of negative sequencing results,gene variant reanalysis can be performed when the patients show clinically suspicious indications.

Adrenocorticotropic hormone combined with magnesium sulfate therapy for infantile epileptic spasms syndrome:a real-world study

Background Infantile epileptic spasms syndrome(IESS)is a serious disease in infants,and it usually evolves to other epilepsy types or syndromes,especially refractory or super-refractory focal epilepsies.Although adrenocorticotropic hormone(ACTH)is one of the first-line and effective treatment plans for IESS,it has serious side effects and is not sufficiently effective.Methods A retrospective study of the clinical outcomes of ACTH combined with magnesium sulfate(MgSO4)therapy for IESS in two hospital centers was conducted.The major outcome of the single and combined treatment was evaluated by changes in seizure frequency and improvements in hypsarrhythmia electroencephalography(EEG).To reduce the confounding bias between the two groups,we used SPSS for the propensity score matching(PSM)analysis.Results We initially recruited 1205 IESS patients from two Chinese hospitals and treated them with ACTH combined with MgSO4 and ACTH alone.Only 1005 patients were enrolled in the treatment(ACTH combined with MgSO4:744,ACTH:261),and both treatment plans had a more than 55%response rate.However,compared to patients treated with ACTH alone,those patients treated with ACTH combined with MgSO4 had better performance in terms of the seizure frequency and hypsarrhythmia EEG.After PSM,the two groups also showed significant differences in responder rate[70.8%(95%confidence interval,CI)=66.7%–74.8%)vs.53.8%(95%CI=47.4%–60.2%),P<0.001],seizure frequency(P<0.001)and hypsarrhythmia EEG resolution(P<0.001).Notably,multivariate analysis revealed that the lead time to treatment and the number of antiseizure medications taken before treatment were two factors that may affect the clinical outcome.Patients with less than 3 months of lead time responded to the treatment much better than those with>3 months(P<0.05).In addition,the overall incidence of adverse reactions in the ACTH combined with MgSO4 group was much lower than that in the ACTH group(31.4%vs.63.1%,P<0.001).During the treatment,only infection(P=0.045)and hypertension(P=0.025)were significantly different between the two groups,and no baby died.Conclusion Our findings support that ACTH combined with MgSO4 is a more effective short-term treatment protocol for patients with IESS than ACTH alone,especially for those patients with short lead times to treatment.