Tay-Sachs disease: case report

Objectives: Report a case of Tay-Sachs disease. Methods: A complete ophthalmologic examination, retinography and blood dosage of hexosaminidase A (EHA) activity were performed. Results: A one year and seven months old male with a history of generalized tonic-clonic seizures, with delayed neuropsychomotor development from the eighth month of life. At the ophthalmologic examination the patient did not fix or follow objects, with bilateral horizontal nystagmus. The fundoscopy revealed an image of “cherry-red spot” in the macula in both eyes. Dosage of EHA activity confirmed diagnosis of Tay-Sachs disease. Conclusion: TaySachs Disease is a genetic disease with an autosomal recessive inheritance pattern characterized by deficiency of EHA activity, leading to the accumulation of sphingolipids in neuronal cells that results in progressive neurological dysfunction. In the retina, there is deposition in the ganglion cells, resulting in the appearance of cherry-red spot macula. There is no curative treatment, aiming at the therapy, only the clinical support in the patient.


INTRODUCTION
Tay-Sachs disease is a neurodegenerative disorder that results in accumulation of a glycosphingolipid (ganglioside GM2) especially in neurons.Its pathophysiology is a partial or total quantitative defect of the enzyme hexosaminidase A, a genetic condition determined by an autosomal recessive pattern. 1 In the first months of life there is minimal or no clinical abnormality, being only identified in the electronic microscopy of the brain and the retina. 2gns and symptoms begin around the 5th month of life characterized by progressive psychomotor retardation, megaencephaly, cherry-red spot, retinal injury, blindness, deafness, paralysis and death between the 3rd and 5th year of life.The ophthalmological changes have been described since 1881 by Warren Tay and shows an unaltered optic nerve, pale-whitish macula well-delimited with a notoriously hyperchromic center in red-brown color.This color contrast draws attention and defines the injury in "cherry-red spot". 3e histological changes that characterize the background in cherry-red spot are due to the intense accumulation of glycosphingolipid in the macula's ganglion cells, which leaves a pale-whitish appearance.On the other hand, foveal depression, which does not contain ganglion cells, maintains the normal retina's red appearance. 4 is important to emphasize that cherry-red spot injury is not pathognomonic of Tay-Sachs disease.Some other metabolic disorders in which there are lipid deposits also have the same fundus, such as generalized gangliosidosis, Niemann-Pick disease, and Fabry disease.

CASE-REPORT
A male patient 1 year and 8 months old, came to us referred from the pediatric clinic due to seizures to investigate systemic disease.He was born at a gestational age of 40 weeks with no intercurrence; parents were healthy and seconds cousins.Mother stated that when the baby was eight months old, it stopped holding its head and was week to move its limbs, by that time it was also observed that he stopped looking and following objects.Since then, the weakness has become more evident.The patient began to present seizures that became more frequent and lasting, reaching 3 to 4 episodes a day.
Psychomotor retardation, muscle weakness, generalized hyperreflexia, was observed in examination.In ophthalmologic exam, patient did not follow objects or fixate the eyes.Ophthalmoscopy revealed chalk-white macular areas with a "cherry-red spot" in the fovea of both eyes (Figure 1).A deficiency of hexosamidase A in the serum disclosed the diagnosis of Tay-Sachs disease.

DISCUSSION
Tay-Sachs disease is due to the accumulation of GM2 trihexosylceramide secondary to the defect of hexosamindase A enzyme, caused by mutation. 5It accumulates predominantly in retinal ganglion cells whereby retina becomes with "chalkwhite" coloration. 3This is typically present early in the disease, is a clue in the diagnosis, thus, it has been detected even in the fetal stage.Progressive loss of neurological function, hyperirrtability, and progressive weakness, loss of motors and intellectual skills at the end of the first year are observed.They may crawl but never walk.The natural course leads to a decerebrate, vegetative stage by second to fourth year of life and death.
A juvenile form of Tay-sachs disease exists, with late onset and slower course but with a similar constellation of signs.An adult form is also described with ataxia, dysarthria, muscle weakness, and dementia.However, inthat form, no "cherryred" spot is seen. 3e diagnosis of Tay-Sachs disease is confirmed by assaying for the activity of individual hexosaminisidase isoenzymes in serum.
Hexosaminidase A deficiency is inherited in the autosomal recessive pattern.Thus, the parents must be heterozygous, since they would not survive to reproductive age in the condition of recessive homozygotes.During conception, therefore, the offspring have a 25% chance of being affected, a 50% chance of being an asymptomatic carrier of the recessive allele and 25% of being neither affected nor the carrier.Couples with a positive history of children with Tay-Sachs should undergo genetic counseling because there is a high risk of this fatal disease repeats in offspring. 1ere are already reliable genetic screening tests for the detection of carriers in high-risk populations, such as in Jewish communities, helping to prevent primary disease. 6rrently, Tay-Sachs disease treatment is signs and symptoms control and clinical support, although enzyme replacement therapies have been introduced for several lysosomal storage, no effective treatment is available.It is important that the patient has adequate hydric and nutritional intake, early identification of secondary infections and airway protection.Seizures should be managed pharmacologically with antiepileptics.As the disease progresses, seizures become more frequent, necessitating changes in drug doses.
Trials with intravenous enzyme replacement therapy were not effective because they could not cross the blood-brain barrier.In vivo studies with rats using intracranial injections containing recombinant viral vectors of hexosaminidase A producing genes are showing promise for the future. 7

Figure 1 .
Figure 1.Retinography revealed an image of "cherry-red spot" in the macula in both eyes.