Multimodal optical imaging and genetic features of AB variant GM2 gangliosidosis: a case report

Abstract

Background: AB variant GM2 gangliosidosis is an extremely rare autosomal recessive lysosomal storage disease. Macular cherry-red spots are the most commonly described ocular sign in this disease. Here, for the first time we report a case of an infant with AB variant GM2 gangliosidosis, along with multimodal optical imaging and genetic testing results.

Case description: A 7-month-old Chinese girl presented to the hospital with nystagmus for 2 months. Her family history for this condition showed negative results, and her parents were not known to be consanguineous. Fundus photography showed a cherry-red spot with a ring of whitish infiltrate surrounding both macula. Fundus fluorescein angiography showed normal retinal circulation and vessels. Optical coherence tomography (OCT) revealed a thickening and increased reflectivity of the inner retinal layers with a shadowing effect on the outer structures. The patient had no obvious neurological symptoms, and the MRI results of the head were normal. The whole-exome genome sequencing results showed that there was a homozygous deletion (chr5: 150639196-150639548) of exon 2 in the GM2A gene. Finally, the patient was diagnosed with AB variant GM2 gangliosidosis.

Conclusions: AB variant GM2 gangliosidosis is a rare disease affecting multiple nervous systems. Before the occurrence of typical neurological symptoms, the clinical features of fundus photography and OCT help us diagnose GM2 gangliosidosis.

Keywords: AB variant GM2 gangliosidosis; cherry-red spot; fundus fluorescein angiography (FFA); gene; optical coherence tomography.

Figure 1

Fundus photography, FFA, and OCT images of the patient. (A,B), a cherry-red spot with a ring of whitish infiltrate within a 1–2 PD area surrounding the fovea (dotted red squares). (C,D) normal retinal vessels without obstruction. (E,F) thickened and increased reflectivity of the inner retinal layers with a shadowing effect on the outer structures (red arrows). It was difficult to distinguish the inner retinal structure.

Figure 2

Exon 2 deletion in GM2A. A schematic representation of the deletion detected in the GM2A gene. The deleted region is represented by dotted lines, whereas the intact region is represented by solid lines. The downward arrows indicate the breakpoints of the deletion.