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Editor,—Tay-Sachs disease is characterised by lesions in the central nervous systems due to the precipitation of GM2 trihexosylceramide in neurocytes.1 Its onset at around 6 months after birth is manifested by mental and emotional retardation together with hypomyotonia and hyperacusis as its typical signs. Subsequently, the patient tends to develop convulsions insidiously and usually dies at 2–4 years of age. A cherry red spot and optic nerve atrophy are the characteristic ophthalmic signs in this disease.
This report deals with observations of a patient with Tay-Sachs disease whose ophthalmic signs were monitored from birth to his death at the age of 5 years 8 months. During this period, a cherry red spot developed and then diminished in both eyes.
The subject was a boy who was born weighing 1600 g at a gestational age of 36 weeks. Two weeks after birth, ophthalmoscopy disclosed a favourable stretch of retinal blood vessels to the peripheral area without any abnormality of the optic disc and macula in both eyes. Following pursuit movement was observed 5 months after birth. Mental and emotional retardations were manifested beginning at 6 months of age which were precipitated with the onset of afebrile tonic convulsions at the age of 1 year 1 month. Following the convulsions, funduscopy revealed chalk-white macular areas with a cherry red spot in the centre of both eyes. Optic atrophy was present in the left eye and mild paleness in the right eye. Nystagmus with no light fixation was present.
Quantitative analysis of plasma cells and cultured skin fibroblasts revealed a deficiency of β hexosaminidase A enzyme. Immunoelectron microscopy of a biopsy specimen from the rectum disclosed lamellar inclusion body positive for anti-GM2 antibody, whereby a diagnosis of Tay-Sachs disease was made.
At the age of 1 year 6 months, no alterations were observed in the cherry red spot in both eyes and the optic nerve atrophy in the left eye. However, optic nerve atrophy was now quite evident in the right eye. Thereafter, there were no funduscopic changes as evidenced in the fundus photograph at the age of 2 years 10 months (Fig 1). At the age of 3 years 4 months, however, ophthalmoscopy revealed that the turbidity in the opaque lesions surrounding the cherry red spot in the retina had decreased slightly. The fundus photograph at the age of 5 years 8 months demonstrates a further reduction in the retinal opacity (Fig 2). The patient died at the age of 5 years 8 months.
The pathogenesis of Tay-Sachs disease is attributable to the accumulation of GM2 trihexosylceramide secondary to defects of β hexosaminidase A enzyme. GM2trihexosylceramide accumulates predominantly in the retinal ganglion cells whereby retina becomes turbid with a milky-white coloration. The pattern of the coloration is in conformity with the density of the ganglion cells. Strong opacity is observed in the macula area which is characterised by the multilayered ganglion cells, and the opacity is not found in the foveal pit that is devoid of ganglion cells. Eventually, a cherry red spot develops. In our patient, the macular opacity, in all likelihood, was induced by the accumulation of GM2 trihexosylceramide in ganglion cells that then decreased over time. It has been reported from cerebral biopsy findings at various phases of this disease that there is a ballooning of the neurons with vacuolisation in the cytoplasm with progression of the disease process.2 Eventually, there is a disappearance of the neurons resulting in gliosis.
The retina is an extension of the central nervous system, and ganglioside fractions parallel those of the brain.3-5 The lipids stored in the ganglion cells of the retina have similar histochemical reactivity in the retina as in the brain. Accordingly, it is postulated that, as with the cerebral neurons, hypertrophy is also observed in the retinal ganglion cells, followed by their death and disappearance over time. Finally, there is proliferation of glia cells. These progressive changes probably account for the alleviation of retinal opacity and the loss of the cherry red spot in our patient.