Clinical and laboratory findings in 3 rare cases from gangliosidosis family

The gangliosidoses comprise a family of lysosomal storage diseases with an autosomal recessive trait characterized by the accumulation of complex glycosphingolipids in the nervous system and other tissues with progressive neurodegeneration and varied clinical presentations and are divided into 2 major groups: GM1 (with 3 clinical subtypes) and GM2 (include Tay-Sachs disease, Sandhoff disease and GM2 activator protein deficiency) gangliosidoses associated with lysosomal enzymatic deficiency of β-galactosidase and respectively hexosaminidase. The GM1 gangliosidoses are characterized by dysostosis, organomegaly and coarsening in their most severe forms, whereas patients with GM2 gangliosidosis Tay-Sachs disease are usually spared systemic involvement, except in the case of the Sandhoff variant, in which organomegaly may occur.

We retrospectively analyzed clinical, biochemical and genetic data of three unrelated patients (one female, two males) from different geographical backgrounds and ethnicity suspected by a neurometabolic condition presented with a spectrum of phenotypic features such as variable neurologic symptoms, ataxia, developmental delay or regression, seizures, coarse facial features, hepatosplenomegaly, cherry red spots, hypoacusia, skin laxity, skeletal manifestations. Diagnosis was confirmed by Whole Exome Sequencing and enzymatic measurement from dried blood spots. Genotype analyses revealed pathogenic or likely pathogenic variants involving GLB1 gene (c.320G>A, c.860C>T, c.597C>A, c.985C>T) and HEXB gene (c.850C>T) and enzyme activity assessment showed a poor residual enzyme activity for β-galactosidase and respectively β-hexosaminidase.

Gangliosidoses represent progressive, multisystem disorders. Genetic study is essential for definite diagnosis. Early diagnosis of the disease is extremely important. The finding that the disease does not have a specific treatment or cure option yet reveals the importance of prenatal diagnosis and genetic counseling.