Genetics Unit, Pediatrics Department, Faculty of Medicine, Ain Shams University, Cairo, EgyptReceived 17 June 2011; accepted 12 July 2011Available online 3 December 2011Part I: Educational caseA 3.5-year-old boy, the second in order of birth of first cousinparents presented to the genetics clinic for counseling. The pa-tient had normal development till the age of 2 years then hestarted to have abnormal ataxic gait with frequent falls. Atthe age of 2.5 years, he started to lose previously acquired cog-nitive skills and speech and to develop convulsions. Neurolog-ical examination showed hypotonia and increased deep tendonreflexes. The patient had a sister and a paternal cousin with thesame clinical picture who both died at the age of 5 and 6 years.MRI brain showed brain atrophy. Fundus examinationshowed cherry-red spot (Fig. 1). The mother is 10 weeks preg-nant and asks about prenatal diagnosis.Q1: What is the most probable diagnosis?The most probable diagnosis is Tay Sachs disease which is aneurodegenerative disorder caused by intralysosomal storageof the specific glycosphingolipid GM2 ganglioside. Commonclinical findings include progressive weakness and loss of mo-tor and cognitive skills, decreased attentiveness and an in-creased startle response. The typical findings on physicalexamination are generalized muscular hypotonia, ankle clonus,hyperreflexia and normal-sized liver and spleen. This is fol-lowed by signs of progressive neurodegeneration, seizures,blindness, and spasticity. A cherry-red spot of the fovea cen-tralis of the macula of the retina is usually found on fundusexamination [1].Our patient has the juvenile (subacute) form. The diseaseoften begins between the age of 2 and 10 years by loss of pre-viously acquired skills and speech followed by spasticity andseizures. Loss of vision occurs much later than in the acuteinfantile form of the disease, and a cherry-red spot – in con-trary to our case – is not consistently observed. Instead, opticatrophy and retinitis pigmentosa may be seen late in thecourse. A vegetative state with decerebrate rigidity developsby age 10–15 years, followed within few years by death, usuallyfrom infection. In some cases, the disease pursues a particu-larly aggressive course, culminating in death in 2–4 years [2].Q2: Are there other phenotypes of the disease?Other phenotypes include [1]: Acute infantile (Tay-Sachs disease) with rapid progressionand death before age 4 years. Chronic and adult-onset Tay Sachs disease with long-termsurvival. Affected individuals have several different pheno-types, including progressive dystonia, spinocerebellardegeneration, motor neuron disease with muscle weaknessand fasciculations, and/or psychosis. ActivatordeficientTaysachsdisease:itisarareinfantileform(phenotype identical to classic disease) where the enzymaticactivityofbothhexosaminidaseA(HEXA)andhexosamin-idase B (HEX B) are normal, but GM2 ganglioside accumu-lation occurs because of a deficit of the intralysosomal