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

TL;DR

A case of Sandhoff disease with infantile epileptic spasm syndrome was identified through reanalysis of genetic data.

Contribution

The study highlights that IESS can be a rare clinical manifestation of Sandhoff disease and the importance of reanalyzing genetic data when clinical suspicion remains.

Findings

A homozygous mutation in the HEXB gene was identified through reanalysis of whole exome sequencing data.

The patient exhibited significantly decreased β-hexosaminidase A and total hexosaminidase activities.

Cherry red spots in the fundus confirmed the diagnosis of Sandhoff disease.

Abstract

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.

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 of β-hexosaminidase A and total hexosaminidase were significantly decreased. The fundus examination showed cherry red spots at the macula.

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.

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