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SynopsisTay-Sachs disease is an autosomal recessive lysosomal storage disorder caused by mutations in the HEXA gene, which encodes for the alpha-subunit of hexosaminidase A. Deficiency of this enzyme results in accumulation of lipids (GM2 ganglioside) in nerve cells. Tay-Sachs disease is primarily seen in the Ashkenazi Jewish population.
In the infantile form, the initial symptom is most often an exaggerated startle response, particularly to loud noises. Other common signs and symptoms include developmental delay, weakness and eventual paralysis, hypertonia, cognitive and motor deterioration, cherry-red macula, vision and hearing loss, seizures, and poor feeding. There is often a characteristic enlargement of the head that occurs between the first and second year of life. The prognosis is poor, and most individuals have a progressive neurologic decline leading to death within the first few years of life.
There are later-onset presentations of Tay-Sachs disease: juvenile- and adult-onset forms. Clinically, there is a slow progression of neurologic symptoms and disability. Juvenile onset frequently presents with coordination difficulties. Adult-onset presentation often includes progressive muscle weakness and atrophy, especially of the legs, along with dysarthria. Cognitive declines in memory and attention along with personality changes, depression, and sometimes psychosis are also prominent.
E75.02 – Tay-Sachs disease
111385000 – Tay-Sachs disease
Differential Diagnosis & PitfallsThere is no hepatosplenomegaly in Tay-Sachs disease, which helps differentiate it from other lysosomal storage disorders.
- Sandhoff disease (hexosaminidase beta subunit deficiency)
- GM1 gangliosidosis
- Krabbe disease (globoid cell leukodystrophy)
- Leigh disease
- Neuronal ceroid lipofuscinosis
- Canavan disease
- Metachromatic leukodystrophy
- Niemann-Pick disease type A
- Gaucher disease type 2
- Amyotrophic lateral sclerosis (ALS)
- Spinocerebellar degeneration
- Kufs disease (adult-onset neuronal ceroid lipofuscinosis)
- Friedreich ataxia
- Spinal muscular atrophy type 3