Rare Variant of GM2 Gangliosidosis through Activator-Protein Deficiency

Abstract

GM2 gangliosidosis, AB variant, is a very rare form of GM2 gangliosidosis due to a deficiency of GM2 activator protein. We report on two patients with typical clinical features suggestive of GM2 gangliosidosis, but normal results for hexosaminidase A and hexosaminidase B as well as their corresponding genes. Genetic analysis of the gene encoding the activator protein, the gene, elucidated the cause of the disease, adding a novel mutation to the spectrum of GM2 AB variant. This report points out that in typical clinical constellations with normal enzyme results, genetic diagnostic for activator protein defects should be performed.

Clinical, Imaging, Genetic, and Disease Course Characteristics in Patients With GM2 Gangliosidosis

“…These 2 patients have been published previously. 20 Time of disease onset in 2 patients, where it had been reported as “early infancy” and “kindergarten,” respectively, was estimated as age 3 years; and in one patient, where it had been reported as “in the first year,” was estimated as age 6 months.…”

“…The following MRI features were identified in patients with GM2 gangliosidosis 20-24 and operationally defined in the study CRF data sheet:Delayed myelination: normal myelination pattern on T1w and T2w images, but delayed for age.Peritrigonal signal hyperintensity on T2w images also covering the optic radiationAtrophy of supratentorial or infratentorial structures (according to Gburek 25 ).Abnormalities of the basal ganglia: swollen appearance with mild hyperintensity on T2w and difficulties in distinguishing the capsula interna from surrounding parenchyma.Hypomyelination, for example, insufficient myelination without progression and a discrepancy between T1-weighted and T2-weighted images (T1w > T2w).…”

“…In early-onset GM2 forms, the characteristic swollen MRI aspect of the diencephalon, especially the basal ganglia, has been well described previously, 21-23 while peritrigonal signal hyperintensity also covering the optic radiation to our knowledge has only been reported by us before in 2 children with GM2 gangliosidosis due to activator deficiency. 20 Early-onset GM2 gangliosidosis has been described as a brain hypomyelination disorder. 23,27 However, in our cohort of GM2 patients, we identified hypomyelination only in one patient with Sandhoff disease.…”

GM2 gangliosidosis AB variant: first case of late onset and review of the literature

“…The visible lesions on brain MRI were extremely similar between patients. Among those for whom clinical signs started at or before 12 months, two showed periventricular and basal ganglia T2 hyper-signals [24,27], three had basal ganglia hypersignal with delayed myelination [26][27][28], and only one did not show any abnormality [29]. Only patients carrying the p.Pro55Leu mutation, in the heterozygous [19] or homozygous state, had brain atrophy without signal alteration [20].…”